segmentmodel.py 131.70 KiB
import pdb
from pathlib import Path
import numpy as np
import random
from .model.arbdmodel import PointParticle, ParticleType, Group, ArbdModel
from .coords import rotationAboutAxis, quaternion_from_matrix, quaternion_to_matrix
from .model.nonbonded import *
from copy import copy, deepcopy
from .model.nbPot import nbDnaScheme
from scipy.special import erf
import scipy.optimize as opt
from scipy import interpolate
from .model.CanonicalNucleotideAtoms import canonicalNtFwd, canonicalNtRev, seqComplement
from .model.CanonicalNucleotideAtoms import enmTemplateHC, enmTemplateSQ, enmCorrectionsHC
from .model.spring_from_lp import k_angle as angle_spring_from_lp
# import pdb
"""
TODO:
+ fix handling of crossovers for atomic representation
+ map to atomic representation
+ add nicks
+ transform ssDNA nucleotides
- shrink ssDNA
+ shrink dsDNA backbone
+ make orientation continuous
+ sequence
+ handle circular dna
+ ensure crossover bead potentials aren't applied twice
+ remove performance bottlenecks
- test for large systems
+ assign sequence
+ ENM
- rework Location class
- remove recursive calls
- document
- develop unit test suite
- refactor parts of Segment into an abstract_polymer class
- make each call generate_bead_model, generate_atomic_model, generate_oxdna_model return an object with only have a reference to original object
"""
class CircularDnaError(Exception):
pass
class ParticleNotConnectedError(Exception):
pass
class Location():
""" Site for connection within an object """
def __init__(self, container, address, type_, on_fwd_strand = True):
## TODO: remove cyclic references(?)
self.container = container
self.address = address # represents position along contour length in segment
# assert( type_ in ("end3","end5") ) # TODO remove or make conditional
self.on_fwd_strand = on_fwd_strand
self.type_ = type_
self.particle = None
self.connection = None
self.is_3prime_side_of_connection = None
self.prev_in_strand = None
self.next_in_strand = None
self.combine = None # some locations might be combined in bead model
def get_connected_location(self):
if self.connection is None:
return None
else:
return self.connection.other(self)
def set_connection(self, connection, is_3prime_side_of_connection):
self.connection = connection # TODO weakref?
self.is_3prime_side_of_connection = is_3prime_side_of_connection
def get_nt_pos(self):
try:
pos = self.container.contour_to_nt_pos(self.address, round_nt=True)
except:
if self.address == 0:
pos = 0
elif self.address == 1:
pos = self.container.num_nt-1
else:
raise
return pos
def __repr__(self):
if self.on_fwd_strand:
on_fwd = "on_fwd_strand"
else:
on_fwd = "on_rev_strand"
return "<Location {}.{}[{:.2f},{:d}]>".format( self.container.name, self.type_, self.address, self.on_fwd_strand)
class Connection():
""" Abstract base class for connection between two elements """
def __init__(self, A, B, type_ = None):
assert( isinstance(A,Location) )
assert( isinstance(B,Location) )
self.A = A
self.B = B
self.type_ = type_
def other(self, location):
if location is self.A:
return self.B
elif location is self.B:
return self.A
else:
raise Exception("OutOfBoundsError")
def delete(self):
self.A.container.connections.remove(self)
if self.B.container is not self.A.container:
self.B.container.connections.remove(self)
self.A.connection = None
self.B.connection = None
def __repr__(self):
return "<Connection {}--{}--{}]>".format( self.A, self.type_, self.B )
# class ConnectableElement(Transformable):
class ConnectableElement():
""" Abstract base class """
def __init__(self, connection_locations=None, connections=None):
if connection_locations is None: connection_locations = []
if connections is None: connections = []
## TODO decide on names
self.locations = self.connection_locations = connection_locations
self.connections = connections
def get_locations(self, type_=None, exclude=()):
locs = [l for l in self.connection_locations if (type_ is None or l.type_ == type_) and l.type_ not in exclude]
counter = dict()
for l in locs:
if l in counter:
counter[l] += 1
else:
counter[l] = 1
assert( np.all( [counter[l] == 1 for l in locs] ) )
return locs
def get_location_at(self, address, on_fwd_strand=True, new_type="crossover"):
loc = None
if (self.num_nt == 1):
# import pdb
# pdb.set_trace()
## Assumes that intrahelical connections have been made before crossovers
for l in self.locations:
if l.on_fwd_strand == on_fwd_strand and l.connection is None:
assert(loc is None)
loc = l
# assert( loc is not None )
else:
for l in self.locations:
if l.address == address and l.on_fwd_strand == on_fwd_strand:
assert(loc is None)
loc = l
if loc is None:
loc = Location( self, address=address, type_=new_type, on_fwd_strand=on_fwd_strand )
return loc
def get_connections_and_locations(self, connection_type=None, exclude=()):
""" Returns a list with each entry of the form:
connection, location_in_self, location_in_other """
type_ = connection_type
ret = []
for c in self.connections:
if (type_ is None or c.type_ == type_) and c.type_ not in exclude:
if c.A.container is self:
ret.append( [c, c.A, c.B] )
elif c.B.container is self:
ret.append( [c, c.B, c.A] )
else:
import pdb
pdb.set_trace()
raise Exception("Object contains connection that fails to refer to object")
return ret
def _connect(self, other, connection, in_3prime_direction=None):
## TODO fix circular references
A,B = [connection.A, connection.B]
if in_3prime_direction is not None:
A.is_3prime_side_of_connection = not in_3prime_direction
B.is_3prime_side_of_connection = in_3prime_direction
A.connection = B.connection = connection
self.connections.append(connection)
if other is not self:
other.connections.append(connection)
else:
raise NotImplementedError("Segments cannot yet be connected to themselves; if you are attempting to make a circular object, try breaking the object into multiple segments")
l = A.container.locations
if A not in l: l.append(A)
l = B.container.locations
if B not in l: l.append(B)
# def _find_connections(self, loc):
# return [c for c in self.connections if c.A == loc or c.B == loc]
class SegmentParticle(PointParticle):
def __init__(self, type_, position, name="A", **kwargs):
self.name = name
self.contour_position = None
PointParticle.__init__(self, type_, position, name=name, **kwargs)
self.intrahelical_neighbors = []
self.other_neighbors = []
self.locations = []
def get_intrahelical_above(self, all_types=True):
""" Returns bead directly above self """
# assert( len(self.intrahelical_neighbors) <= 2 )
for b in self.intrahelical_neighbors:
if b.get_contour_position(self.parent, self.contour_position) > self.contour_position:
if all_types or isinstance(b,type(self)):
return b
def get_intrahelical_below(self, all_types=True):
""" Returns bead directly below self """
# assert( len(self.intrahelical_neighbors) <= 2 )
for b in self.intrahelical_neighbors:
if b.get_contour_position(self.parent, self.contour_position) < self.contour_position:
if all_types or isinstance(b,type(self)):
return b
def _neighbor_should_be_added(self,b):
if type(self.parent) != type(b.parent):
return True
c1 = self.contour_position
c2 = b.get_contour_position(self.parent,c1)
if c2 < c1:
b0 = self.get_intrahelical_below()
else:
b0 = self.get_intrahelical_above()
if b0 is not None:
c0 = b0.get_contour_position(self.parent,c1)
if np.abs(c2-c1) < np.abs(c0-c1):
## remove b0
self.intrahelical_neighbors.remove(b0)
b0.intrahelical_neighbors.remove(self)
return True
else:
return False
return True
def make_intrahelical_neighbor(self,b):
add1 = self._neighbor_should_be_added(b)
add2 = b._neighbor_should_be_added(self)
if add1 and add2:
# assert(len(b.intrahelical_neighbors) <= 1)
# assert(len(self.intrahelical_neighbors) <= 1)
self.intrahelical_neighbors.append(b)
b.intrahelical_neighbors.append(self)
def conceptual_get_position(self, context):
"""
context: object
Q: does this function do too much?
Danger of mixing return values
Q: does context describe the system or present an argument?
"""
## Validate Inputs
...
## Algorithm
"""
context specifies:
- kind of output: real space, nt within segment, fraction of segment
- absolute or relative
- constraints: e.g. if passing through
"""
"""
given context, provide the position
input
"""
def get_nt_position(self, seg, near_address=None):
""" Returns the "address" of the nucleotide relative to seg in
nucleotides, taking the shortest (intrahelical) contour length route to seg
"""
if seg == self.parent:
pos = self.contour_position
else:
pos = self.get_contour_position(seg,near_address)
return seg.contour_to_nt_pos(pos)
def get_contour_position(self,seg, address = None):
""" TODO: fix paradigm where a bead maps to exactly one location in a polymer
- One way: modify get_contour_position to take an optional argument that indicates where in the polymer you are looking from
"""
if seg == self.parent:
return self.contour_position
else:
cutoff = 30*3
target_seg = seg
## depth-first search
## TODO cache distances to nearby locations?
def descend_search_tree(seg, contour_in_seg, distance=0, visited_segs=None):
nonlocal cutoff
if visited_segs is None: visited_segs = []
if seg == target_seg:
# pdb.set_trace()
## Found a segment in our target
sign = 1 if contour_in_seg == 1 else -1
if sign == -1: assert( contour_in_seg == 0 )
if distance < cutoff: # TODO: check if this does anything
cutoff = distance
return [[distance, contour_in_seg+sign*seg.nt_pos_to_contour(distance)]], [(seg, contour_in_seg, distance)]
if distance > cutoff:
return None,None
ret_list = []
hist_list = []
## Find intrahelical locations in seg that we might pass through
conn_locs = seg.get_connections_and_locations("intrahelical")
if isinstance(target_seg, SingleStrandedSegment):
tmp = seg.get_connections_and_locations("sscrossover")
conn_locs = conn_locs + list(filter(lambda x: x[2].container == target_seg, tmp))
for c,A,B in conn_locs:
if B.container in visited_segs: continue
dx = seg.contour_to_nt_pos( A.address, round_nt=False ) - seg.contour_to_nt_pos( contour_in_seg, round_nt=False)
dx = np.abs(dx)
results,history = descend_search_tree( B.container, B.address,
distance+dx, visited_segs + [seg] )
if results is not None:
ret_list.extend( results )
hist_list.extend( history )
return ret_list,hist_list
results,history = descend_search_tree(self.parent, self.contour_position)
if results is None or len(results) == 0:
raise Exception("Could not find location in segment") # TODO better error
if address is not None:
return sorted(results,key=lambda x:(x[0],(x[1]-address)**2))[0][1]
else:
return sorted(results,key=lambda x:x[0])[0][1]
# nt_pos = self.get_nt_position(seg)
# return seg.nt_pos_to_contour(nt_pos)
def update_position(self, contour_position):
self.contour_position = contour_position
self.position = self.parent.contour_to_position(contour_position)
if 'orientation_bead' in self.__dict__:
o = self.orientation_bead
o.contour_position = contour_position
orientation = self.parent.contour_to_orientation(contour_position)
if orientation is None:
print("WARNING: local_twist is True, but orientation is None; using identity")
orientation = np.eye(3)
o.position = self.position + orientation.dot( np.array((Segment.orientation_bond.r0,0,0)) )
def __repr__(self):
return "<SegmentParticle {} on {}[{:.2f}]>".format( self.name, self.parent, self.contour_position)
## TODO break this class into smaller, better encapsulated pieces
class Segment(ConnectableElement, Group):
""" Base class that describes a segment of DNA. When built from
cadnano models, should not span helices """
"""Define basic particle types"""
dsDNA_particle = ParticleType("D",
diffusivity = 43.5,
mass = 300,
radius = 3,
)
orientation_particle = ParticleType("O",
diffusivity = 100,
mass = 300,
radius = 1,
)
# orientation_bond = HarmonicBond(10,2)
orientation_bond = HarmonicBond(30,1.5, rRange = (0,500) )
ssDNA_particle = ParticleType("S",
diffusivity = 43.5,
mass = 150,
radius = 3,
)
def __init__(self, name, num_nt,
start_position = None,
end_position = None,
segment_model = None,
**kwargs):
if start_position is None: start_position = np.array((0,0,0))
Group.__init__(self, name, children=[], **kwargs)
ConnectableElement.__init__(self, connection_locations=[], connections=[])
if 'segname' not in kwargs:
self.segname = name
# self.resname = name
self.start_orientation = None
self.twist_per_nt = 0
self.beads = [c for c in self.children] # self.beads will not contain orientation beads
self._bead_model_generation = 0 # TODO: remove?
self.segment_model = segment_model # TODO: remove?
self.strand_pieces = dict()
for d in ('fwd','rev'):
self.strand_pieces[d] = []
self.num_nt = int(num_nt)
if end_position is None:
end_position = np.array((0,0,self.distance_per_nt*num_nt)) + start_position
self.start_position = start_position
self.end_position = end_position
## Used to assign cadnano names to beads
self._generate_bead_callbacks = []
self._generate_nucleotide_callbacks = []
## Set up interpolation for positions
self._set_splines_from_ends()
self.sequence = None
def __repr__(self):
return "<{} {}[{:d}]>".format( type(self), self.name, self.num_nt )
def set_splines(self, contours, coords):
tck, u = interpolate.splprep( coords.T, u=contours, s=0, k=1)
self.position_spline_params = (tck,u)
def set_orientation_splines(self, contours, quaternions):
tck, u = interpolate.splprep( quaternions.T, u=contours, s=0, k=1)
self.quaternion_spline_params = (tck,u)
def get_center(self):
tck, u = self.position_spline_params
return np.mean(self.contour_to_position(u), axis=0)
def _get_location_positions(self):
return [self.contour_to_nt_pos(l.address) for l in self.locations]
def insert_dna(self, at_nt: int, num_nt: int, seq=tuple()):
assert(np.isclose(np.around(num_nt),num_nt))
if at_nt < 0:
raise ValueError("Attempted to insert DNA into {} at a negative location".format(self))
if at_nt > self.num_nt-1:
raise ValueError("Attempted to insert DNA into {} at beyond the end of the Segment".format(self))
if num_nt < 0:
raise ValueError("Attempted to insert DNA a negative amount of DNA into {}".format(self))
num_nt = np.around(num_nt)
nt_positions = self._get_location_positions()
new_nt_positions = [p if p <= at_nt else p+num_nt for p in nt_positions]
## TODO: handle sequence
self.num_nt = self.num_nt+num_nt
for l,p in zip(self.locations, new_nt_positions):
l.address = self.nt_pos_to_contour(p)
def remove_dna(self, first_nt: int, last_nt: int):
""" Removes nucleotides between first_nt and last_nt, inclusive """
assert(np.isclose(np.around(first_nt),first_nt))
assert(np.isclose(np.around(last_nt),last_nt))
tmp = min((first_nt,last_nt))
last_nt = max((first_nt,last_nt))
fist_nt = tmp
if first_nt < 0 or first_nt > self.num_nt-2:
raise ValueError("Attempted to remove DNA from {} starting at an invalid location {}".format(self, first_nt))
if last_nt < 1 or last_nt > self.num_nt-1:
raise ValueError("Attempted to remove DNA from {} ending at an invalid location {}".format(self, last_nt))
if first_nt == last_nt:
return
first_nt = np.around(first_nt)
last_nt = np.around(last_nt)
nt_positions = self._get_location_positions()
bad_locations = list(filter(lambda p: p >= first_nt and p <= last_nt, nt_positions))
if len(bad_locations) > 0:
raise Exception("Attempted to remove DNA containing locations {} from {} between {} and {}".format(bad_locations,self,first_nt,last_nt))
removed_nt = last_nt-first_nt+1
new_nt_positions = [p if p <= last_nt else p-removed_nt for p in nt_positions]
num_nt = self.num_nt-removed_nt
if self.sequence is not None and len(self.sequence) == self.num_nt:
self.sequence = [s for s,i in zip(self.sequence,range(self.num_nt))
if i < first_nt or i > last_nt]
assert( len(self.sequence) == num_nt )
self.num_nt = num_nt
for l,p in zip(self.locations, new_nt_positions):
l.address = self.nt_pos_to_contour(p)
def __filter_contours(contours, positions, position_filter, contour_filter):
u = contours
r = positions
## Filter
ids = list(range(len(u)))
if contour_filter is not None:
ids = list(filter(lambda i: contour_filter(u[i]), ids))
if position_filter is not None:
ids = list(filter(lambda i: position_filter(r[i,:]), ids))
return ids
def translate(self, translation_vector, position_filter=None, contour_filter=None):
dr = np.array(translation_vector)
tck, u = self.position_spline_params
r = self.contour_to_position(u)
ids = Segment.__filter_contours(u, r, position_filter, contour_filter)
if len(ids) == 0: return
## Translate
r[ids,:] = r[ids,:] + dr[np.newaxis,:]
self.set_splines(u,r)
def rotate(self, rotation_matrix, about=None, position_filter=None, contour_filter=None):
tck, u = self.position_spline_params
r = self.contour_to_position(u)
ids = Segment.__filter_contours(u, r, position_filter, contour_filter)
if len(ids) == 0: return
if about is None:
## TODO: do this more efficiently
r[ids,:] = np.array([rotation_matrix.dot(r[i,:]) for i in ids])
else:
dr = np.array(about)
## TODO: do this more efficiently
r[ids,:] = np.array([rotation_matrix.dot(r[i,:]-dr) + dr for i in ids])
self.set_splines(u,r)
if self.quaternion_spline_params is not None:
## TODO: performance: don't shift between quaternion and matrix representations so much
tck, u = self.quaternion_spline_params
orientations = [self.contour_to_orientation(v) for v in u]
for i in ids:
orientations[i,:] = rotation_matrix.dot(orientations[i])
quats = [quaternion_from_matrix(o) for o in orientations]
self.set_orientation_splines(u, quats)
def _set_splines_from_ends(self, resolution=4):
self.quaternion_spline_params = None
r0 = np.array(self.start_position)[np.newaxis,:]
r1 = np.array(self.end_position)[np.newaxis,:]
u = np.linspace(0,1, max(3,self.num_nt//int(resolution)))
s = u[:,np.newaxis]
coords = (1-s)*r0 + s*r1
self.set_splines(u, coords)
def clear_all(self):
Group.clear_all(self) # TODO: use super?
self.beads = []
# for c,loc,other in self.get_connections_and_locations():
# loc.particle = None
# other.particle = None
for l in self.locations:
l.particle = None
def contour_to_nt_pos(self, contour_pos, round_nt=False):
nt = contour_pos*(self.num_nt) - 0.5
if round_nt:
assert( np.isclose(np.around(nt),nt) )
nt = np.around(nt)
return nt
def nt_pos_to_contour(self,nt_pos):
return (nt_pos+0.5)/(self.num_nt)
def contour_to_position(self,s):
p = interpolate.splev( s, self.position_spline_params[0] )
if len(p) > 1: p = np.array(p).T
return p
def contour_to_tangent(self,s):
t = interpolate.splev( s, self.position_spline_params[0], der=1 )
t = (t / np.linalg.norm(t,axis=0))
return t.T
def contour_to_orientation(self,s):
assert( isinstance(s,float) or isinstance(s,int) or len(s) == 1 ) # TODO make vectorized version
if self.quaternion_spline_params is None:
axis = self.contour_to_tangent(s)
axis = axis / np.linalg.norm(axis)
rotAxis = np.cross(axis,np.array((0,0,1)))
rotAxisL = np.linalg.norm(rotAxis)
zAxis = np.array((0,0,1))
if rotAxisL > 0.001:
theta = np.arcsin(rotAxisL) * 180/np.pi
if axis.dot(zAxis) < 0: theta = 180-theta
orientation0 = rotationAboutAxis( rotAxis/rotAxisL, theta, normalizeAxis=False ).T
else:
orientation0 = np.eye(3) if axis.dot(zAxis) > 0 else \
rotationAboutAxis( np.array((1,0,0)), 180, normalizeAxis=False )
if self.start_orientation is not None:
orientation0 = orientation0.dot(self.start_orientation)
orientation = rotationAboutAxis( axis, self.twist_per_nt*self.contour_to_nt_pos(s), normalizeAxis=False )
orientation = orientation.dot(orientation0)
else:
q = interpolate.splev( s, self.quaternion_spline_params[0] )
if len(q) > 1: q = np.array(q).T # TODO: is this needed?
orientation = quaternion_to_matrix(q)
return orientation
def get_contour_sorted_connections_and_locations(self,type_):
sort_fn = lambda c: c[1].address
cl = self.get_connections_and_locations(type_)
return sorted(cl, key=sort_fn)
def randomize_unset_sequence(self):
bases = list(seqComplement.keys())
# bases = ['T'] ## FOR DEBUG
if self.sequence is None:
self.sequence = [random.choice(bases) for i in range(self.num_nt)]
else:
assert(len(self.sequence) == self.num_nt) # TODO move
for i in range(len(self.sequence)):
if self.sequence[i] is None:
self.sequence[i] = random.choice(bases)
def _get_num_beads(self, max_basepairs_per_bead, max_nucleotides_per_bead ):
raise NotImplementedError
def _generate_one_bead(self, contour_position, nts):
raise NotImplementedError
def _generate_atomic_nucleotide(self, contour_position, is_fwd, seq, scale, strand_segment):
""" Seq should include modifications like 5T, T3 Tsinglet; direction matters too """
# print("Generating nucleotide at {}".format(contour_position))
pos = self.contour_to_position(contour_position)
orientation = self.contour_to_orientation(contour_position)
""" deleteme
## TODO: move this code (?)
if orientation is None:
import pdb
pdb.set_trace()
axis = self.contour_to_tangent(contour_position)
angleVec = np.array([1,0,0])
if axis.dot(angleVec) > 0.9: angleVec = np.array([0,1,0])
angleVec = angleVec - angleVec.dot(axis)*axis
angleVec = angleVec/np.linalg.norm(angleVec)
y = np.cross(axis,angleVec)
orientation = np.array([angleVec,y,axis]).T
## TODO: improve placement of ssDNA
# rot = rotationAboutAxis( axis, contour_position*self.twist_per_nt*self.num_nt, normalizeAxis=True )
# orientation = rot.dot(orientation)
else:
orientation = orientation
"""
key = seq
nt_dict = canonicalNtFwd if is_fwd else canonicalNtRev
atoms = nt_dict[ key ].generate() # TODO: clone?
atoms.orientation = orientation.dot(atoms.orientation)
if isinstance(self, SingleStrandedSegment):
if scale is not None and scale != 1:
for a in atoms:
a.position = scale*a.position
atoms.position = pos - atoms.atoms_by_name["C1'"].collapsedPosition()
else:
if scale is not None and scale != 1:
if atoms.sequence in ("A","G"):
r0 = atoms.atoms_by_name["N9"].position
else:
r0 = atoms.atoms_by_name["N1"].position
for a in atoms:
if a.name[-1] in ("'","P","T"):
a.position = scale*(a.position-r0) + r0
else:
a.fixed = 1
atoms.position = pos
atoms.contour_position = contour_position
strand_segment.add(atoms)
for callback in self._generate_nucleotide_callbacks:
callback(atoms)
return atoms
def _generate_oxdna_nucleotide(self, contour_position, is_fwd, seq):
bp_center = self.contour_to_position(contour_position)
orientation = self.contour_to_orientation(contour_position)
DefaultOrientation = rotationAboutAxis([0,0,1], 90)
if is_fwd:
DefaultOrientation = rotationAboutAxis([1,0,0], 180).dot(DefaultOrientation)
o = orientation.dot(DefaultOrientation)
if isinstance(self, SingleStrandedSegment):
pos = bp_center
else:
pos = bp_center - 5*o.dot(np.array((1,0,0)))
nt = PointParticle("oxdna_nt", position= pos,
orientation = o)
nt.contour_position = contour_position
return nt
def add_location(self, nt, type_, on_fwd_strand=True):
## Create location if needed, add to segment
c = self.nt_pos_to_contour(nt)
assert(c >= 0 and c <= 1)
# TODO? loc = self.Location( address=c, type_=type_, on_fwd_strand=is_fwd )
loc = Location( self, address=c, type_=type_, on_fwd_strand=on_fwd_strand )
self.locations.append(loc)
## TODO? Replace with abstract strand-based model?
def add_nick(self, nt, on_fwd_strand=True):
self.add_3prime(nt,on_fwd_strand)
self.add_5prime(nt+1,on_fwd_strand)
def add_5prime(self, nt, on_fwd_strand=True):
if isinstance(self,SingleStrandedSegment):
on_fwd_strand = True
self.add_location(nt,"5prime",on_fwd_strand)
def add_3prime(self, nt, on_fwd_strand=True):
if isinstance(self,SingleStrandedSegment):
on_fwd_strand = True
self.add_location(nt,"3prime",on_fwd_strand)
def get_3prime_locations(self):
return sorted(self.get_locations("3prime"),key=lambda x: x.address)
def get_5prime_locations(self):
## TODO? ensure that data is consistent before _build_model calls
return sorted(self.get_locations("5prime"),key=lambda x: x.address)
def iterate_connections_and_locations(self, reverse=False):
## connections to other segments
cl = self.get_contour_sorted_connections_and_locations()
if reverse:
cl = cl[::-1]
for c in cl:
yield c
## TODO rename
def _add_strand_piece(self, strand_piece):
""" Registers a strand segment within this object """
## TODO use weakref
d = 'fwd' if strand_piece.is_fwd else 'rev'
## Validate strand_piece (ensure no clashes)
for s in self.strand_pieces[d]:
l,h = sorted((s.start,s.end))
for value in (strand_piece.start,strand_piece.end):
assert( value < l or value > h )
## Add strand_piece in correct order
self.strand_pieces[d].append(strand_piece)
self.strand_pieces[d] = sorted(self.strand_pieces[d],
key = lambda x: x.start)
## TODO rename
def get_strand_segment(self, nt_pos, is_fwd, move_at_least=0.5):
""" Walks through locations, checking for crossovers """
# if self.name in ("6-1","1-1"):
# import pdb
# pdb.set_trace()
move_at_least = 0
## Iterate through locations
# locations = sorted(self.locations, key=lambda l:(l.address,not l.on_fwd_strand), reverse=(not is_fwd))
def loc_rank(l):
nt = l.get_nt_pos()
## optionally add logic about type of connection
return (nt, not l.on_fwd_strand)
# locations = sorted(self.locations, key=lambda l:(l.address,not l.on_fwd_strand), reverse=(not is_fwd))
locations = sorted(self.locations, key=loc_rank, reverse=(not is_fwd))
# print(locations)
for l in locations:
# TODOTODO probably okay
if l.address == 0:
pos = 0.0
elif l.address == 1:
pos = self.num_nt-1
else:
pos = self.contour_to_nt_pos(l.address, round_nt=True)
## DEBUG
## Skip locations encountered before our strand
# tol = 0.1
# if is_fwd:
# if pos-nt_pos <= tol: continue
# elif nt_pos-pos <= tol: continue
if (pos-nt_pos)*(2*is_fwd-1) < move_at_least: continue
## TODO: remove move_at_least
if np.isclose(pos,nt_pos):
if l.is_3prime_side_of_connection: continue
## Stop if we found the 3prime end
if l.on_fwd_strand == is_fwd and l.type_ == "3prime" and l.connection is None:
# print(" found end at",l)
return pos, None, None, None, None
## Check location connections
c = l.connection
if c is None: continue
B = c.other(l)
## Found a location on the same strand?
if l.on_fwd_strand == is_fwd:
# print(" passing through",l)
# print("from {}, connection {} to {}".format(nt_pos,l,B))
Bpos = B.get_nt_pos()
return pos, B.container, Bpos, B.on_fwd_strand, 0.5
## Stop at other strand crossovers so basepairs line up
elif c.type_ == "crossover":
if nt_pos == pos: continue
# print(" pausing at",l)
return pos, l.container, pos+(2*is_fwd-1), is_fwd, 0
raise Exception("Shouldn't be here")
# print("Shouldn't be here")
## Made it to the end of the segment without finding a connection
return 1*is_fwd, None, None, None
def get_nearest_bead(self, contour_position):
if len(self.beads) < 1: return None
cs = np.array([b.contour_position for b in self.beads]) # TODO: cache
# TODO: include beads in connections?
i = np.argmin((cs - contour_position)**2)
return self.beads[i]
def _get_atomic_nucleotide(self, nucleotide_idx, is_fwd=True):
d = 'fwd' if is_fwd else 'rev'
for s in self.strand_pieces[d]:
try:
return s.get_nucleotide(nucleotide_idx)
except:
pass
raise Exception("Could not find nucleotide in {} at {}.{}".format( self, nucleotide_idx, d ))
def get_all_consecutive_beads(self, number):
assert(number >= 1)
## Assume that consecutive beads in self.beads are bonded
ret = []
for i in range(len(self.beads)-number+1):
tmp = [self.beads[i+j] for j in range(0,number)]
ret.append( tmp )
return ret
def _add_bead(self,b):
# assert(b.parent is None)
if b.parent is not None:
b.parent.children.remove(b)
self.add(b)
self.beads.append(b) # don't add orientation bead
if "orientation_bead" in b.__dict__: # TODO: think of a cleaner approach
o = b.orientation_bead
o.contour_position = b.contour_position
if o.parent is not None:
o.parent.children.remove(o)
self.add(o)
self.add_bond(b,o, Segment.orientation_bond, exclude=True)
def _rebuild_children(self, new_children):
# print("_rebuild_children on %s" % self.name)
old_children = self.children
old_beads = self.beads
self.children = []
self.beads = []
if True:
## TODO: remove this if duplicates are never found
# print("Searching for duplicate particles...")
## Remove duplicates, preserving order
tmp = []
for c in new_children:
if c not in tmp:
tmp.append(c)
else:
print(" DUPLICATE PARTICLE FOUND!")
new_children = tmp
for b in new_children:
self.beads.append(b)
self.children.append(b)
if "orientation_bead" in b.__dict__: # TODO: think of a cleaner approach
self.children.append(b.orientation_bead)
# tmp = [c for c in self.children if c not in old_children]
# assert(len(tmp) == 0)
# tmp = [c for c in old_children if c not in self.children]
# assert(len(tmp) == 0)
assert(len(old_children) == len(self.children))
assert(len(old_beads) == len(self.beads))
def _generate_beads(self, bead_model, max_basepairs_per_bead, max_nucleotides_per_bead):
""" Generate beads (positions, types, etc) and bonds, angles, dihedrals, exclusions """
## TODO: decide whether to remove bead_model argument
## (currently unused)
## First find points between-which beads must be generated
# conn_locs = self.get_contour_sorted_connections_and_locations()
# locs = [A for c,A,B in conn_locs]
# existing_beads = [l.particle for l in locs if l.particle is not None]
# if self.name == "S001":
# pdb.set_trace()
# pdb.set_trace()
existing_beads0 = { (l.particle, l.particle.get_contour_position(self,l.address))
for l in self.locations if l.particle is not None }
existing_beads = sorted( list(existing_beads0), key=lambda bc: bc[1] )
# if self.num_nt == 1 and all([l.particle is not None for l in self.locations]):
# pdb.set_trace()
# return
for b,c in existing_beads:
assert(b.parent is not None)
## Add ends if they don't exist yet
## TODOTODO: test 1 nt segments?
if len(existing_beads) == 0 or existing_beads[0][0].get_nt_position(self,0) >= 0.5:
# if len(existing_beads) > 0:
# assert(existing_beads[0].get_nt_position(self) >= 0.5)
c = self.nt_pos_to_contour(0)
if self.num_nt == 1: c -= 0.4
b = self._generate_one_bead(c, 0)
existing_beads = [(b,0)] + existing_beads
if existing_beads[-1][0].get_nt_position(self,1)-(self.num_nt-1) < -0.5 or len(existing_beads)==1:
c = self.nt_pos_to_contour(self.num_nt-1)
if self.num_nt == 1: c += 0.4
b = self._generate_one_bead(c, 0)
existing_beads.append( (b,1) )
assert(len(existing_beads) > 1)
## Walk through existing_beads, add beads between
tmp_children = [] # build list of children in nice order
last = None
for I in range(len(existing_beads)-1):
eb1,eb2 = [existing_beads[i][0] for i in (I,I+1)]
ec1,ec2 = [existing_beads[i][1] for i in (I,I+1)]
assert( (eb1,ec1) is not (eb2,ec2) )
# if np.isclose(eb1.position[2], eb2.position[2]):
# import pdb
# pdb.set_trace()
# print(" %s working on %d to %d" % (self.name, eb1.position[2], eb2.position[2]))
e_ds = ec2-ec1
num_beads = self._get_num_beads( e_ds, max_basepairs_per_bead, max_nucleotides_per_bead )
## Ensure there is a ssDNA bead between dsDNA beads
if num_beads == 0 and isinstance(self,SingleStrandedSegment) and isinstance(eb1.parent,DoubleStrandedSegment) and isinstance(eb2.parent,DoubleStrandedSegment):
num_beads = 1
## TODO similarly ensure there is a dsDNA bead between ssDNA beads
ds = e_ds / (num_beads+1)
nts = ds*self.num_nt
eb1.num_nt += 0.5*nts
eb2.num_nt += 0.5*nts
## Add beads
if eb1.parent == self:
tmp_children.append(eb1)
s0 = ec1
if last is not None:
last.make_intrahelical_neighbor(eb1)
last = eb1
for j in range(num_beads):
s = ds*(j+1) + s0
# if self.name in ("51-2","51-3"):
# if self.name in ("31-2",):
# print(" adding bead at {}".format(s))
b = self._generate_one_bead(s,nts)
last.make_intrahelical_neighbor(b)
last = b
tmp_children.append(b)
last.make_intrahelical_neighbor(eb2)
if eb2.parent == self:
tmp_children.append(eb2)
# if self.name in ("31-2",):
# pdb.set_trace()
self._rebuild_children(tmp_children)
for callback in self._generate_bead_callbacks:
callback(self)
def _regenerate_beads(self, max_nts_per_bead=4, ):
...
class DoubleStrandedSegment(Segment):
""" Class that describes a segment of ssDNA. When built from
cadnano models, should not span helices """
def __init__(self, name, num_bp, start_position = np.array((0,0,0)),
end_position = None,
segment_model = None,
local_twist = False,
num_turns = None,
start_orientation = None,
twist_persistence_length = 90,
**kwargs):
self.helical_rise = 10.44
self.distance_per_nt = 3.4
Segment.__init__(self, name, num_bp,
start_position,
end_position,
segment_model,
**kwargs)
self.num_bp = self.num_nt
self.local_twist = local_twist
if num_turns is None:
num_turns = float(num_bp) / self.helical_rise
self.twist_per_nt = float(360 * num_turns) / num_bp
if start_orientation is None:
start_orientation = np.eye(3) # np.array(((1,0,0),(0,1,0),(0,0,1)))
self.start_orientation = start_orientation
self.twist_persistence_length = twist_persistence_length
self.nicks = []
self.start = self.start5 = Location( self, address=0, type_= "end5" )
self.start3 = Location( self, address=0, type_ = "end3", on_fwd_strand=False )
self.end = self.end3 = Location( self, address=1, type_ = "end3" )
self.end5 = Location( self, address=1, type_= "end5", on_fwd_strand=False )
# for l in (self.start5,self.start3,self.end3,self.end5):
# self.locations.append(l)
## TODO: initialize sensible spline for orientation
## Convenience methods
## TODO: add errors if unrealistic connections are made
## TODO: make connections automatically between unconnected strands
def connect_start5(self, end3, type_="intrahelical", force_connection=False):
if isinstance(end3, SingleStrandedSegment):
end3 = end3.end3
self._connect_ends( self.start5, end3, type_, force_connection = force_connection )
def connect_start3(self, end5, type_="intrahelical", force_connection=False):
if isinstance(end5, SingleStrandedSegment):
end5 = end5.start5
self._connect_ends( self.start3, end5, type_, force_connection = force_connection )
def connect_end3(self, end5, type_="intrahelical", force_connection=False):
if isinstance(end5, SingleStrandedSegment):
end5 = end5.start5
self._connect_ends( self.end3, end5, type_, force_connection = force_connection )
def connect_end5(self, end3, type_="intrahelical", force_connection=False):
if isinstance(end3, SingleStrandedSegment):
end3 = end3.end3
self._connect_ends( self.end5, end3, type_, force_connection = force_connection )
def add_crossover(self, nt, other, other_nt, strands_fwd=(True,False), nt_on_5prime=True, type_="crossover"):
""" Add a crossover between two helices """
## Validate other, nt, other_nt
## TODO
if isinstance(other,SingleStrandedSegment):
other.add_crossover(other_nt, self, nt, strands_fwd[::-1], not nt_on_5prime)
else:
## Create locations, connections and add to segments
c = self.nt_pos_to_contour(nt)
assert(c >= 0 and c <= 1)
loc = self.get_location_at(c, strands_fwd[0])
c = other.nt_pos_to_contour(other_nt)
# TODOTODO: may need to subtract or add a little depending on 3prime/5prime
assert(c >= 0 and c <= 1)
other_loc = other.get_location_at(c, strands_fwd[1])
self._connect(other, Connection( loc, other_loc, type_=type_ ))
if nt_on_5prime:
loc.is_3prime_side_of_connection = False
other_loc.is_3prime_side_of_connection = True
else:
loc.is_3prime_side_of_connection = True
other_loc.is_3prime_side_of_connection = False
## Real work
def _connect_ends(self, end1, end2, type_, force_connection):
debug = False
## TODO remove self?
## validate the input
for end in (end1, end2):
assert( isinstance(end, Location) )
assert( end.type_ in ("end3","end5") )
assert( end1.type_ != end2.type_ )
## Remove other connections involving these points
if end1.connection is not None:
if debug: print("WARNING: reconnecting {}".format(end1))
end1.connection.delete()
if end2.connection is not None:
if debug: print("WARNING: reconnecting {}".format(end2))
end2.connection.delete()
## Create and add connection
if end2.type_ == "end5":
end1.container._connect( end2.container, Connection( end1, end2, type_=type_ ), in_3prime_direction=True )
else:
end2.container._connect( end1.container, Connection( end2, end1, type_=type_ ), in_3prime_direction=True )
def _get_num_beads(self, contour, max_basepairs_per_bead, max_nucleotides_per_bead):
# return int(contour*self.num_nt // max_basepairs_per_bead)
return int(contour*(self.num_nt**2/(self.num_nt+1)) // max_basepairs_per_bead)
def _generate_one_bead(self, contour_position, nts):
pos = self.contour_to_position(contour_position)
if self.local_twist:
orientation = self.contour_to_orientation(contour_position)
if orientation is None:
print("WARNING: local_twist is True, but orientation is None; using identity")
orientation = np.eye(3)
opos = pos + orientation.dot( np.array((Segment.orientation_bond.r0,0,0)) )
# if np.linalg.norm(pos) > 1e3:
# pdb.set_trace()
assert(np.linalg.norm(opos-pos) < 10 )
o = SegmentParticle( Segment.orientation_particle, opos, name="O",
contour_position = contour_position,
num_nt=nts, parent=self )
bead = SegmentParticle( Segment.dsDNA_particle, pos, name="DNA",
num_nt=nts, parent=self,
orientation_bead=o,
contour_position=contour_position )
else:
bead = SegmentParticle( Segment.dsDNA_particle, pos, name="DNA",
num_nt=nts, parent=self,
contour_position=contour_position )
self._add_bead(bead)
return bead
class SingleStrandedSegment(Segment):
""" Class that describes a segment of ssDNA. When built from
cadnano models, should not span helices """
def __init__(self, name, num_nt, start_position = None,
end_position = None,
segment_model = None,
**kwargs):
if start_position is None: start_position = np.array((0,0,0))
self.distance_per_nt = 5
Segment.__init__(self, name, num_nt,
start_position,
end_position,
segment_model,
**kwargs)
self.start = self.start5 = Location( self, address=0, type_= "end5" ) # TODO change type_?
self.end = self.end3 = Location( self, address=1, type_ = "end3" )
# for l in (self.start5,self.end3):
# self.locations.append(l)
def connect_end3(self, end5, force_connection=False):
self._connect_end( end5, _5_to_3 = True, force_connection = force_connection )
def connect_start5(self, end3, force_connection=False):
self._connect_end( end3, _5_to_3 = False, force_connection = force_connection )
def connect_5end(self, end3, force_connection=False): # TODO: change name or possibly deprecate
print("WARNING: 'connect_5end' will be deprecated")
return self.connect_start5( end3, force_connection=False)
def _connect_end(self, other, _5_to_3, force_connection):
assert( isinstance(other, Location) )
if _5_to_3 == True:
seg1 = self
seg2 = other.container
end1 = self.end3
end2 = other
assert(other.type_ != "end3")
# if (other.type_ is not "end5"):
# print("WARNING: code does not prevent connecting 3prime to 3prime, etc")
else:
seg1 = other.container
seg2 = self
end1 = other
end2 = self.start
assert(other.type_ != "end5")
# if (other.type_ is not "end3"):
# print("WARNING: code does not prevent connecting 3prime to 3prime, etc")
## Remove other connections involving these points
if end1.connection is not None:
print("WARNING: reconnecting {}".format(end1))
end1.connection.delete()
if end2.connection is not None:
print("WARNING: reconnecting {}".format(end2))
end2.connection.delete()
conn = Connection( end1, end2, type_="intrahelical" )
seg1._connect( seg2, conn, in_3prime_direction=True )
def add_crossover(self, nt, other, other_nt, strands_fwd=(True,False), nt_on_5prime=True, type_='sscrossover'):
""" Add a crossover between two helices """
## TODO Validate other, nt, other_nt
assert(nt < self.num_nt)
assert(other_nt < other.num_nt)
if nt in (0,1,self.num_nt-1) and other_nt in (0,1,other.num_nt-1):
if nt_on_5prime == True:
other_end = other.start5 if strands_fwd[1] else other.end5
self.connect_end3( other_end )
else:
other_end = other.end3 if strands_fwd[1] else other.start3
self.connect_start5( other_end )
return
# c1 = self.nt_pos_to_contour(nt)
# # TODOTODO
# ## Ensure connections occur at ends, otherwise the structure doesn't make sense
# # assert(np.isclose(c1,0) or np.isclose(c1,1))
# assert(np.isclose(nt,0) or np.isclose(nt,self.num_nt-1))
if nt == 0 and (self.num_nt > 1 or not nt_on_5prime):
c1 = 0
elif nt == self.num_nt-1:
c1 = 1
else:
raise Exception("Crossovers can only be at the ends of an ssDNA segment")
loc = self.get_location_at(c1, True)
if other_nt == 0:
c2 = 0
elif other_nt == other.num_nt-1:
c2 = 1
else:
c2 = other.nt_pos_to_contour(other_nt)
if isinstance(other,SingleStrandedSegment):
## Ensure connections occur at opposing ends
assert(np.isclose(other_nt,0) or np.isclose(other_nt,self.num_nt-1))
other_loc = other.get_location_at( c2, True )
# if ("22-2" in (self.name, other.name)):
# pdb.set_trace()
if nt_on_5prime:
self.connect_end3( other_loc )
else:
other.connect_end3( self )
else:
assert(c2 >= 0 and c2 <= 1)
other_loc = other.get_location_at( c2, strands_fwd[1] )
if nt_on_5prime:
self._connect(other, Connection( loc, other_loc, type_="sscrossover" ), in_3prime_direction=True )
else:
other._connect(self, Connection( other_loc, loc, type_="sscrossover" ), in_3prime_direction=True )
def _get_num_beads(self, contour, max_basepairs_per_bead, max_nucleotides_per_bead):
return int(contour*(self.num_nt**2/(self.num_nt+1)) // max_basepairs_per_bead)
# return int(contour*self.num_nt // max_nucleotides_per_bead)
def _generate_one_bead(self, contour_position, nts):
pos = self.contour_to_position(contour_position)
b = SegmentParticle( Segment.ssDNA_particle, pos,
name="NAS",
num_nt=nts, parent=self,
contour_position=contour_position )
self._add_bead(b)
return b
class StrandInSegment(Group):
""" Represents a piece of an ssDNA strand within a segment """
def __init__(self, segment, start, end, is_fwd):
""" start/end should be provided expressed in nt coordinates, is_fwd tuples """
Group.__init__(self)
self.num_nt = 0
# self.sequence = []
self.segment = segment
self.start = start
self.end = end
self.is_fwd = is_fwd
nts = np.abs(end-start)+1
self.num_nt = int(round(nts))
assert( np.isclose(self.num_nt,nts) )
segment._add_strand_piece(self)
def _nucleotide_ids(self):
nt0 = self.start # seg.contour_to_nt_pos(self.start)
assert( np.abs(nt0 - round(nt0)) < 1e-5 )
nt0 = int(round(nt0))
assert( (self.end-self.start) >= 0 or not self.is_fwd )
direction = (2*self.is_fwd-1)
return range(nt0,nt0 + direction*self.num_nt, direction)
def get_sequence(self):
""" return 5-to-3 """
# TODOTODO test
seg = self.segment
if self.is_fwd:
return [seg.sequence[nt] for nt in self._nucleotide_ids()]
else:
return [seqComplement[seg.sequence[nt]] for nt in self._nucleotide_ids()]
def get_contour_points(self):
c0,c1 = [self.segment.nt_pos_to_contour(p) for p in (self.start,self.end)]
return np.linspace(c0,c1,self.num_nt)
def get_nucleotide(self, idx):
""" idx expressed as nt coordinate within segment """
lo,hi = sorted((self.start,self.end))
if self.is_fwd:
idx_in_strand = idx - lo
else:
idx_in_strand = hi - idx
assert( np.isclose( idx_in_strand , int(round(idx_in_strand)) ) )
assert(idx_in_strand >= 0)
return self.children[int(round(idx_in_strand))]
def __repr__(self):
return "<StrandInSegment {}{}[{:.2f}-{:.2f},{:d}]>".format( self.parent.segname, self.segment.name, self.start, self.end, self.is_fwd)
class Strand(Group):
""" Represents an entire ssDNA strand from 5' to 3' as it routes through segments """
def __init__(self, segname = None, is_circular = False):
Group.__init__(self)
self.num_nt = 0
self.children = self.strand_segments = []
self.oxdna_nt = []
self.segname = segname
self.is_circular = is_circular
self.debug = False
def __repr__(self):
return "<Strand {}({})>".format( self.segname, self.num_nt )
## TODO disambiguate names of functions
def add_dna(self, segment, start, end, is_fwd):
""" start/end are given as nt """
if np.abs(start-end) <= 0.9:
if self.debug:
print( "WARNING: segment constructed with a very small number of nts ({})".format(np.abs(start-end)) )
# import pdb
# pdb.set_trace()
for s in self.strand_segments:
if s.segment == segment and s.is_fwd == is_fwd:
# assert( s.start not in (start,end) )
# assert( s.end not in (start,end) )
if s.start in (start,end) or s.end in (start,end):
raise CircularDnaError("Found circular DNA")
s = StrandInSegment( segment, start, end, is_fwd )
self.add( s )
self.num_nt += s.num_nt
def set_sequence(self,sequence): # , set_complement=True):
## validate input
assert( len(sequence) >= self.num_nt )
assert( np.all( [i in ('A','T','C','G') for i in sequence] ) )
seq_idx = 0
## set sequence on each segment
for s in self.children:
seg = s.segment
if seg.sequence is None:
seg.sequence = [None for i in range(seg.num_nt)]
if s.is_fwd:
for nt in s._nucleotide_ids():
seg.sequence[nt] = sequence[seq_idx]
seq_idx += 1
else:
for nt in s._nucleotide_ids():
seg.sequence[nt] = seqComplement[sequence[seq_idx]]
seq_idx += 1
# def get_sequence(self):
# sequence = []
# for ss in self.strand_segments:
# sequence.extend( ss.get_sequence() )
# assert( len(sequence) >= self.num_nt )
# ret = ["5"+sequence[0]] +\
# sequence[1:-1] +\
# [sequence[-1]+"3"]
# assert( len(ret) == self.num_nt )
# return ret
def link_nucleotides(self, nt5, nt3):
parent = nt5.parent if nt5.parent is nt3.parent else self
o3,c3,c4,c2,h3 = [nt5.atoms_by_name[n]
for n in ("O3'","C3'","C4'","C2'","H3'")]
p,o5,o1,o2,c5 = [nt3.atoms_by_name[n]
for n in ("P","O5'","O1P","O2P","C5'")]
parent.add_bond( o3, p, None )
parent.add_angle( c3, o3, p, None )
for x in (o5,o1,o2):
parent.add_angle( o3, p, x, None )
parent.add_dihedral(c3, o3, p, x, None )
for x in (c4,c2,h3):
parent.add_dihedral(x, c3, o3, p, None )
parent.add_dihedral(o3, p, o5, c5, None)
def generate_atomic_model(self, scale, first_atomic_index):
last = None
resid = 1
## TODO relabel "strand_segment"
strand_segment_count = 0
for s in self.strand_segments:
strand_segment_count += 1
seg = s.segment
contour = s.get_contour_points()
# if s.end == s.start:
# pdb.set_trace()
# assert(s.end != s.start)
assert( s.num_nt == 1 or (np.linalg.norm( seg.contour_to_position(contour[-1]) - seg.contour_to_position(contour[0]) ) > 0.1) )
nucleotide_count = 0
for c,seq in zip(contour,s.get_sequence()):
nucleotide_count += 1
if last is None and not self.is_circular:
seq = "5"+seq
if strand_segment_count == len(s.strand_segments) and nucleotide_count == s.num_nt and not self.is_circular:
seq = seq+"3"
nt = seg._generate_atomic_nucleotide( c, s.is_fwd, seq, scale, s )
## Join last basepairs
if last is not None:
self.link_nucleotides(last,nt)
nt.__dict__['resid'] = resid
resid += 1
last = nt
nt._first_atomic_index = first_atomic_index
first_atomic_index += len(nt.children)
if self.is_circular:
self.link_nucleotides(last,self.strand_segments[0].children[0])
return first_atomic_index
def generate_atomic_model(self, scale, first_atomic_index):
last = None
resid = 1
## TODO relabel "strand_segment"
strand_segment_count = 0
for s in self.strand_segments:
strand_segment_count += 1
seg = s.segment
contour = s.get_contour_points()
# if s.end == s.start:
# pdb.set_trace()
# assert(s.end != s.start)
assert( s.num_nt == 1 or (np.linalg.norm( seg.contour_to_position(contour[-1]) - seg.contour_to_position(contour[0]) ) > 0.1) )
nucleotide_count = 0
for c,seq in zip(contour,s.get_sequence()):
nucleotide_count += 1
if last is None and not self.is_circular:
seq = "5"+seq
if strand_segment_count == len(s.strand_segments) and nucleotide_count == s.num_nt and not self.is_circular:
seq = seq+"3"
nt = seg._generate_atomic_nucleotide( c, s.is_fwd, seq, scale, s )
## Join last basepairs
if last is not None:
self.link_nucleotides(last,nt)
nt.__dict__['resid'] = resid
resid += 1
last = nt
nt._first_atomic_index = first_atomic_index
first_atomic_index += len(nt.children)
if self.is_circular:
self.link_nucleotides(last,self.strand_segments[0].children[0])
return first_atomic_index
def generate_oxdna_model(self):
for s in self.strand_segments:
seg = s.segment
contour = s.get_contour_points()
assert( s.num_nt == 1 or (np.linalg.norm( seg.contour_to_position(contour[-1]) - seg.contour_to_position(contour[0]) ) > 0.1) )
for c,seq in zip(contour,s.get_sequence()):
nt = seg._generate_oxdna_nucleotide( c, s.is_fwd, seq )
self.oxdna_nt.append(nt)
class SegmentModel(ArbdModel):
def __init__(self, segments=[], local_twist=True, escapable_twist=True,
max_basepairs_per_bead=7,
max_nucleotides_per_bead=4,
dimensions=(1000,1000,1000), temperature=291,
timestep=50e-6, cutoff=50,
decompPeriod=10000, pairlistDistance=None,
nonbondedResolution=0,DEBUG=0):
self.DEBUG = DEBUG
if DEBUG > 0: print("Building ARBD Model")
ArbdModel.__init__(self,segments,
dimensions, temperature, timestep, cutoff,
decompPeriod, pairlistDistance=None,
nonbondedResolution=0)
# self.max_basepairs_per_bead = max_basepairs_per_bead # dsDNA
# self.max_nucleotides_per_bead = max_nucleotides_per_bead # ssDNA
self.children = self.segments = segments
self._generate_bead_callbacks = []
self._bonded_potential = dict() # cache for bonded potentials
self._generate_strands()
self.grid_potentials = []
self._generate_bead_model( max_basepairs_per_bead, max_nucleotides_per_bead, local_twist, escapable_twist)
self.useNonbondedScheme( nbDnaScheme )
self.useTclForces = False
def get_connections(self,type_=None,exclude=()):
""" Find all connections in model, without double-counting """
added=set()
ret=[]
for s in self.segments:
items = [e for e in s.get_connections_and_locations(type_,exclude=exclude) if e[0] not in added]
added.update([e[0] for e in items])
ret.extend( list(sorted(items,key=lambda x: x[1].address)) )
return ret
def _recursively_get_beads_within_bonds(self,b1,bonds,done=()):
ret = []
done = list(done)
done.append(b1)
if bonds == 0:
return [[]]
for b2 in b1.intrahelical_neighbors:
if b2 in done: continue
for tmp in self._recursively_get_beads_within_bonds(b2, bonds-1, done):
ret.append( [b2]+tmp )
return ret
def _get_intrahelical_beads(self,num=2):
## TODO: add check that this is not called before adding intrahelical_neighbors in _generate_bead_model
assert(num >= 2)
ret = []
for s in self.segments:
for b1 in s.beads:
for bead_list in self._recursively_get_beads_within_bonds(b1, num-1):
assert(len(bead_list) == num-1)
if b1.idx < bead_list[-1].idx: # avoid double-counting
ret.append([b1]+bead_list)
return ret
def _get_intrahelical_angle_beads(self):
return self._get_intrahelical_beads(num=3)
def _get_potential(self, type_, kSpring, d, max_potential = None):
key = (type_, kSpring, d, max_potential)
if key not in self._bonded_potential:
assert( kSpring >= 0 )
if type_ == "bond":
self._bonded_potential[key] = HarmonicBond(kSpring,d, rRange=(0,1200), max_potential=max_potential)
elif type_ == "angle":
self._bonded_potential[key] = HarmonicAngle(kSpring,d, max_potential=max_potential)
# , resolution = 1, maxForce=0.1)
elif type_ == "dihedral":
self._bonded_potential[key] = HarmonicDihedral(kSpring,d, max_potential=max_potential)
else:
raise Exception("Unhandled potential type '%s'" % type_)
return self._bonded_potential[key]
def get_bond_potential(self, kSpring, d):
assert( d > 0.2 )
return self._get_potential("bond", kSpring, d)
def get_angle_potential(self, kSpring, d):
return self._get_potential("angle", kSpring, d)
def get_dihedral_potential(self, kSpring, d, max_potential=None):
while d > 180: d-=360
while d < -180: d+=360
return self._get_potential("dihedral", kSpring, d, max_potential)
def _getParent(self, *beads ):
if np.all( [b1.parent == b2.parent
for b1,b2 in zip(beads[:-1],beads[1:])] ):
return beads[0].parent
else:
return self
def _get_twist_spring_constant(self, sep):
""" sep in nt """
kT = 0.58622522 # kcal/mol
twist_persistence_length = 90 # set semi-arbitrarily as there is a large spread in literature
## <cos(q)> = exp(-s/Lp) = integrate( cos[x] exp(-A x^2), {x, 0, pi} ) / integrate( exp(-A x^2), {x, 0, pi} )
## Assume A is small
## int[B_] := Normal[Integrate[ Series[Cos[x] Exp[-B x^2], {B, 0, 1}], {x, 0, \[Pi]}]/
## Integrate[Series[Exp[-B x^2], {B, 0, 1}], {x, 0, \[Pi]}]]
## Actually, without assumptions I get fitFun below
## From http://www.annualreviews.org/doi/pdf/10.1146/annurev.bb.17.060188.001405
## units "3e-19 erg cm/ 295 k K" "nm" =~ 73
Lp = twist_persistence_length/0.34
fitFun = lambda x: np.real(erf( (4*np.pi*x + 1j)/(2*np.sqrt(x)) )) * np.exp(-1/(4*x)) / erf(2*np.sqrt(x)*np.pi) - np.exp(-sep/Lp)
k = opt.leastsq( fitFun, x0=np.exp(-sep/Lp) )
return k[0][0] * 2*kT*0.00030461742
def extend(self, other, copy=True, include_strands=False):
assert( isinstance(other, SegmentModel) )
if copy:
for s in other.segments:
self.segments.append(deepcopy(s))
if include_strands:
for s in other.strands:
self.strands.append(deepcopy(s))
else:
for s in other.segments:
self.segments.append(s)
if include_strands:
for s in other.strands:
self.strands.append(s)
self._clear_beads()
def update(self, segment , copy=False):
assert( isinstance(segment, Segment) )
if copy:
segment = deepcopy(segment)
self.segments.append(segment)
self._clear_beads()
""" Mapping between different resolution models """
def clear_atomic(self):
for strand in self.strands:
for s in strand.children:
s.clear_all()
s.oxdna_nt = []
for seg in self.segments:
for d in ('fwd','rev'):
seg.strand_pieces[d] = []
self._generate_strands()
## Clear sequence if needed
for seg in self.segments:
if seg.sequence is not None and len(seg.sequence) != seg.num_nt:
seg.sequence = None
def clear_beads(self):
return self._clear_beads()
def _clear_beads(self):
## TODO: deprecate
for s in self.segments:
try:
s.clear_all()
except:
...
self.clear_all(keep_children=True)
try:
if len(self.strands[0].children[0].children) > 0:
self.clear_atomic()
except:
...
## Check that it worked
assert( len([b for b in self]) == 0 )
locParticles = []
for s in self.segments:
for c,A,B in s.get_connections_and_locations():
for l in (A,B):
if l.particle is not None:
locParticles.append(l.particle)
assert( len(locParticles) == 0 )
assert( len([b for s in self.segments for b in s.beads]) == 0 )
def _update_segment_positions(self, bead_coordinates):
print("WARNING: called deprecated command '_update_segment_positions; use 'update_splines' instead")
return self.update_splines(bead_coordinates)
## Operations on spline coordinates
def translate(self, translation_vector, position_filter=None):
for s in self.segments:
s.translate(translation_vector, position_filter=position_filter)
def rotate(self, rotation_matrix, about=None, position_filter=None):
for s in self.segments:
s.rotate(rotation_matrix, about=about, position_filter=position_filter)
def get_center(self, include_ssdna=False):
if include_ssdna:
segments = self.segments
else:
segments = list(filter(lambda s: isinstance(s,DoubleStrandedSegment),
self.segments))
centers = [s.get_center() for s in segments]
weights = [s.num_nt*2 if isinstance(s,DoubleStrandedSegment) else s.num_nt for s in segments]
# centers,weights = [np.array(a) for a in (centers,weights)]
return np.average( centers, axis=0, weights=weights)
def update_splines(self, bead_coordinates):
""" Set new function for each segments functions
contour_to_position and contour_to_orientation """
for s in self.segments:
# if s.name == "61-1":
# pdb.set_trace()
cabs = s.get_connections_and_locations("intrahelical")
if isinstance(s,SingleStrandedSegment):
cabs = cabs + [[c,A,B] for c,A,B in s.get_connections_and_locations("sscrossover") if A.address == 0 or A.address == 1]
if np.any( [B.particle is None for c,A,B in cabs] ):
print( "WARNING: none type found in connection, skipping" )
cabs = [e for e in cabs if e[2].particle is not None]
def get_beads_and_contour_positions(s):
ret_list = []
def zip_bead_contour(beads,address=None):
if isinstance(address,list):
assert(False)
for b,a in zip(beads,address):
if b is None: continue
try:
ret_list.append((b, b.get_contour_position(s,a)))
except:
...
else:
for b in beads:
if b is None: continue
try:
ret_list.append((b, b.get_contour_position(s,address)))
except:
...
return ret_list
## Add beads from segment s
beads_contours = zip_bead_contour(s.beads)
beads_contours.extend( zip_bead_contour([A.particle for c,A,B in cabs]) )
beads = set([b for b,c in beads_contours])
## Add nearby beads
for c,A,B in cabs:
## TODOTODO test?
filter_fn = lambda x: x is not None and x not in beads
bs = list( filter( filter_fn, B.particle.intrahelical_neighbors ) )
beads_contours.extend( zip_bead_contour( bs, A.address ) )
beads.update(bs)
for i in range(3):
bs = list( filter( filter_fn, [n for b in bs for n in b.intrahelical_neighbors] ) )
beads_contours.extend( zip_bead_contour( bs, A.address ) )
beads.update(bs)
beads_contours = list(set(beads_contours))
beads = list(beads)
## Skip beads that are None (some locations were not assigned a particle to avoid double-counting)
# beads = [b for b in beads if b is not None]
assert( np.any([b is None for b,c in beads_contours]) == False )
# beads = list(filter(lambda x: x[0] is not None, beads))
if isinstance(s, DoubleStrandedSegment):
beads_contours = list(filter(lambda x: x[0].type_.name[0] == "D", beads_contours))
return beads_contours
beads_contours = get_beads_and_contour_positions(s)
contours = [c for b,c in beads_contours]
contours = np.array(contours, dtype=np.float16) # deliberately use low precision
contours,ids1 = np.unique(contours, return_index=True)
beads_contours = [beads_contours[i] for i in ids1]
assert( np.any( (contours[:-1] - contours[1:])**2 >= 1e-8 ) )
## TODO: keep closest beads beyond +-1.5 if there are fewer than 2 beads
tmp = []
dist = 1
while len(tmp) < 5 and dist < 3:
tmp = list(filter(lambda bc: np.abs(bc[1]-0.5) < dist, beads_contours))
dist += 0.1
if len(tmp) <= 1:
raise Exception("Failed to fit spline into segment {}".format(s))
beads = [b for b,c in tmp]
contours = [c for b,c in tmp]
ids = [b.idx for b in beads]
if len(beads) <= 1:
pdb.set_trace()
""" Get positions """
positions = bead_coordinates[ids,:].T
# print("BEADS NOT IN {}:".format(s))
# for b,c in filter(lambda z: z[0] not in s.beads, zip(beads,contours)):
# print(" {}[{:03f}]: {:0.3f}".format(b.parent.name, b.contour_position, c) )
tck, u = interpolate.splprep( positions, u=contours, s=0, k=1 )
# if len(beads) < 8:
# ret = interpolate.splprep( positions, u=contours, s=0, k=1, full_output=1 )
# tck = ret[0][0]
# if ret[2] > 0:
# pdb.set_trace()
# else:
# try:
# ret = interpolate.splprep( positions, u=contours, s=0, k=3, full_output=1 )
# tck = ret[0][0]
# if ret[2] > 0:
# pdb.set_trace()
# except:
# ret = interpolate.splprep( positions, u=contours, s=0, k=1, full_output=1 )
# tck = ret[0][0]
# if ret[2] > 0:
# pdb.set_trace()
s.position_spline_params = (tck,u)
""" Get orientation """
def get_orientation_vector(bead,tangent):
if 'orientation_bead' in bead.__dict__:
o = bead.orientation_bead
oVec = bead_coordinates[o.idx,:] - bead_coordinates[bead.idx,:]
oVec = oVec - oVec.dot(tangent)*tangent
oVec = oVec/np.linalg.norm(oVec)
else:
oVec = None
return oVec
def remove_tangential_projection(vector, tangent):
""" Assume tangent is normalized """
v = vector - vector.dot(tangent)*tangent
return v/np.linalg.norm(v)
def get_orientation_vector(bead,tangent):
if 'orientation_bead' in bead.__dict__:
o = bead.orientation_bead
oVec = bead_coordinates[o.idx,:] - bead_coordinates[bead.idx,:]
oVec = remove_tangential_projection(oVec,tangent)
else:
oVec = None
return oVec
def get_previous_idx_if_none(list_):
previous = None
result = []
i = 0
for e in list_:
if e is None:
result.append(previous)
else:
previous = i
i+=1
return result
def get_next_idx_if_none(list_):
tmp = get_previous_idx_if_none(list_[::-1])[::-1]
return [ len(list_)-1-idx if idx is not None else idx for idx in tmp ]
def fill_in_orientation_vectors(contours,orientation_vectors,tangents):
result = []
last_idx = get_previous_idx_if_none( orientation_vectors )
next_idx = get_next_idx_if_none( orientation_vectors )
none_idx = 0
for c,ov,t in zip(contours,orientation_vectors,tangents):
if ov is not None:
result.append(ov)
else:
p = last_idx[none_idx]
n = next_idx[none_idx]
none_idx += 1
if p is None:
if n is None:
## Should be quite rare; give something random if it happens
print("WARNING: unable to interpolate orientation")
o = np.array((1,0,0))
result.append( remove_tangential_projection(o,t) )
else:
o = orientation_vectors[n]
result.append( remove_tangential_projection(o,t) )
else:
if n is None:
o = orientation_vectors[p]
result.append( remove_tangential_projection(o,t) )
else:
cp,cn = [contours[i] for i in (p,n)]
op,on = [orientation_vectors[i] for i in (p,n)]
if (cn-cp) > 1e-6:
o = ((cn-c)*op+(c-cp)*on)/(cn-cp)
else:
o = op+on
result.append( remove_tangential_projection(o,t) )
return result
tangents = s.contour_to_tangent(contours)
orientation_vectors = [get_orientation_vector(b,t) for b,t in zip(beads,tangents)]
if len(beads) > 3 and any([e is not None for e in orientation_vectors] ):
orientation_vectors = fill_in_orientation_vectors(contours, orientation_vectors, tangents)
quats = []
lastq = None
for b,t,oVec in zip(beads,tangents,orientation_vectors):
y = np.cross(t,oVec)
assert( np.abs(np.linalg.norm(y) - 1) < 1e-2 )
q = quaternion_from_matrix( np.array([oVec,y,t]).T)
if lastq is not None:
if q.dot(lastq) < 0:
q = -q
quats.append( q )
lastq = q
# pdb.set_trace()
quats = np.array(quats)
# tck, u = interpolate.splprep( quats.T, u=contours, s=3, k=3 ) ;# cubic spline not as good
tck, u = interpolate.splprep( quats.T, u=contours, s=0, k=1 )
s.quaternion_spline_params = (tck,u)
def _generate_bead_model(self,
max_basepairs_per_bead = 7,
max_nucleotides_per_bead = 4,
local_twist=False,
escapable_twist=True):
## TODO: deprecate
self.generate_bead_model( max_basepairs_per_bead = max_basepairs_per_bead,
max_nucleotides_per_bead = max_nucleotides_per_bead,
local_twist=local_twist,
escapable_twist=escapable_twist)
def generate_bead_model(self,
max_basepairs_per_bead = 7,
max_nucleotides_per_bead = 4,
local_twist=False,
escapable_twist=True):
self.children = self.segments # is this okay?
self.clear_beads()
segments = self.segments
for s in segments:
s.local_twist = local_twist
""" Simplify connections """
# d_nt = dict() #
# for s in segments:
# d_nt[s] = 1.5/(s.num_nt-1)
# for s in segments:
# ## replace consecutive crossovers with
# cl = sorted( s.get_connections_and_locations("crossover"), key=lambda x: x[1].address )
# last = None
# for entry in cl:
# c,A,B = entry
# if last is not None and \
# (A.address - last[1].address) < d_nt[s]:
# same_type = c.type_ == last[0].type_
# same_dest_seg = B.container == last[2].container
# if same_type and same_dest_seg:
# if np.abs(B.address - last[2].address) < d_nt[B.container]:
# ## combine
# A.combine = last[1]
# B.combine = last[2]
# ...
# # if last is not None:
# # s.bead_locations.append(last)
# ...
# last = entry
# del d_nt
""" Generate beads at intrahelical junctions """
if self.DEBUG: print( "Adding intrahelical beads at junctions" )
## Loop through all connections, generating beads at appropriate locations
for c,A,B in self.get_connections("intrahelical"):
s1,s2 = [l.container for l in (A,B)]
assert( A.particle is None )
assert( B.particle is None )
## TODO: offload the work here to s1
# TODOTODO
a1,a2 = [l.address for l in (A,B)]
for a in (a1,a2):
assert( np.isclose(a,0) or np.isclose(a,1) )
## TODO improve this for combinations of ssDNA and dsDNA (maybe a1/a2 should be calculated differently)
""" Search to see whether bead at location is already found """
b = None
if isinstance(s1,DoubleStrandedSegment):
b = s1.get_nearest_bead(a1)
if b is not None:
assert( b.parent is s1 )
""" if above assertion is true, no problem here """
if np.abs(b.get_nt_position(s1) - s1.contour_to_nt_pos(a1)) > 0.5:
b = None
if b is None and isinstance(s2,DoubleStrandedSegment):
b = s2.get_nearest_bead(a2)
if b is not None:
if np.abs(b.get_nt_position(s2) - s2.contour_to_nt_pos(a2)) > 0.5:
b = None
if b is not None and b.parent not in (s1,s2):
b = None
if b is None:
## need to generate a bead
if isinstance(s2,DoubleStrandedSegment):
b = s2._generate_one_bead(a2,0)
else:
b = s1._generate_one_bead(a1,0)
A.particle = B.particle = b
b.is_intrahelical = True
b.locations.extend([A,B])
# pdb.set_trace()
""" Generate beads at other junctions """
for c,A,B in self.get_connections(exclude="intrahelical"):
s1,s2 = [l.container for l in (A,B)]
if A.particle is not None and B.particle is not None:
continue
# assert( A.particle is None )
# assert( B.particle is None )
## TODO: offload the work here to s1/s2 (?)
a1,a2 = [l.address for l in (A,B)]
def maybe_add_bead(location, seg, address, ):
if location.particle is None:
b = seg.get_nearest_bead(address)
try:
distance = seg.contour_to_nt_pos(np.abs(b.contour_position-address))
max_distance = min(max_basepairs_per_bead, max_nucleotides_per_bead)*0.5
if "is_intrahelical" in b.__dict__:
max_distance = 0.5
if distance >= max_distance:
raise Exception("except")
## combine beads
b.update_position( 0.5*(b.contour_position + address) ) # avg position
except:
b = seg._generate_one_bead(address,0)
location.particle = b
b.locations.append(location)
maybe_add_bead(A,s1,a1)
maybe_add_bead(B,s2,a2)
""" Some tests """
for c,A,B in self.get_connections("intrahelical"):
for l in (A,B):
if l.particle is None: continue
assert( l.particle.parent is not None )
""" Generate beads in between """
if self.DEBUG: print("Generating beads")
for s in segments:
s._generate_beads( self, max_basepairs_per_bead, max_nucleotides_per_bead )
# """ Combine beads at junctions as needed """
# for c,A,B in self.get_connections():
# ...
# ## Debug
# all_beads = [b for s in segments for b in s.beads]
# positions = np.array([b.position for b in all_beads])
# dists = positions[:,np.newaxis,:] - positions[np.newaxis,:,:]
# ids = np.where( np.sum(dists**2,axis=-1) + 0.02**2*np.eye(len(dists)) < 0.02**2 )
# print( ids )
# pdb.set_trace()
""" Add intrahelical neighbors at connections """
for c,A,B in self.get_connections("intrahelical"):
b1,b2 = [l.particle for l in (A,B)]
if b1 is b2:
## already handled by Segment._generate_beads
pass
else:
for b in (b1,b2): assert( b is not None )
b1.make_intrahelical_neighbor(b2)
""" Reassign bead types """
if self.DEBUG: print("Assigning bead types")
beadtype_s = dict()
beadtype_count = dict(D=0,O=0,S=0)
def _assign_bead_type(bead, num_nt, decimals):
num_nt0 = bead.num_nt
bead.num_nt = np.around( np.float32(num_nt), decimals=decimals )
char = bead.type_.name[0].upper()
key = (char, bead.num_nt)
if key in beadtype_s:
bead.type_ = beadtype_s[key]
else:
t = deepcopy(bead.type_)
t.__dict__["nts"] = bead.num_nt*2 if char in ("D","O") else bead.num_nt
# t.name = t.name + "%03d" % (t.nts*10**decimals)
t.name = char + "%03d" % (beadtype_count[char])
t.mass = t.nts * 150
t.diffusivity = 120 if t.nts == 0 else min( 50 / np.sqrt(t.nts/5), 120)
beadtype_count[char] += 1
if self.DEBUG: print( "{} --> {} ({})".format(num_nt0, bead.num_nt, t.name) )
beadtype_s[key] = bead.type_ = t
# (cluster_size[c-1])
import scipy.cluster.hierarchy as hcluster
beads = [b for s in segments for b in s if b.type_.name[0].upper() in ("D","O")]
data = np.array([b.num_nt for b in beads])[:,np.newaxis]
order = int(2-np.log10(2*max_basepairs_per_bead)//1)
try:
clusters = hcluster.fclusterdata(data, float(max_basepairs_per_bead)/500, criterion="distance")
cluster_size = [np.mean(data[clusters == i]) for i in np.unique(clusters)]
except:
clusters = np.arange(len(data))+1
cluster_size = data.flatten()
for b,c in zip(beads,clusters):
_assign_bead_type(b, cluster_size[c-1], decimals=order)
beads = [b for s in segments for b in s if b.type_.name[0].upper() in ("S")]
data = np.array([b.num_nt for b in beads])[:,np.newaxis]
order = int(2-np.log10(max_nucleotides_per_bead)//1)
try:
clusters = hcluster.fclusterdata(data, float(max_nucleotides_per_bead)/500, criterion="distance")
cluster_size = [np.mean(data[clusters == i]) for i in np.unique(clusters)]
except:
clusters = np.arange(len(data))+1
cluster_size = data.flatten()
for b,c in zip(beads,clusters):
_assign_bead_type(b, cluster_size[c-1], decimals=order)
self._apply_grid_potentials_to_beads(beadtype_s)
# for bead in [b for s in segments for b in s]:
# num_nt0 = bead.num_nt
# # bead.num_nt = np.around( np.float32(num_nt), decimals=decimals )
# key = (bead.type_.name[0].upper(), bead.num_nt)
# if key in beadtype_s:
# bead.type_ = beadtype_s[key]
# else:
# t = deepcopy(bead.type_)
# t.__dict__["nts"] = bead.num_nt*2 if t.name[0].upper() in ("D","O") else bead.num_nt
# # t.name = t.name + "%03d" % (t.nts*10**decimals)
# t.name = t.name + "%.16f" % (t.nts)
# print( "{} --> {} ({})".format(num_nt0, bead.num_nt, t.name) )
# beadtype_s[key] = bead.type_ = t
""" Update bead indices """
self._countParticleTypes() # probably not needed here
self._updateParticleOrder()
""" Add intrahelical bond potentials """
if self.DEBUG: print("Adding intrahelical bond potentials")
dists = dict() # intrahelical distances built for later use
intra_beads = self._get_intrahelical_beads()
if self.DEBUG: print(" Adding %d bonds" % len(intra_beads))
for b1,b2 in intra_beads:
# assert( not np.isclose( np.linalg.norm(b1.collapsedPosition() - b2.collapsedPosition()), 0 ) )
if np.linalg.norm(b1.collapsedPosition() - b2.collapsedPosition()) < 1:
# print("WARNING: some beads are very close")
...
parent = self._getParent(b1,b2)
## TODO: could be sligtly smarter about sep
sep = 0.5*(b1.num_nt+b2.num_nt)
conversion = 0.014393265 # units "pN/AA" kcal_mol/AA^2
if b1.type_.name[0] == "D" and b2.type_.name[0] == "D":
elastic_modulus_times_area = 1000 # pN http://markolab.bmbcb.northwestern.edu/marko/Cocco.CRP.02.pdf
d = 3.4*sep
k = conversion*elastic_modulus_times_area/d
else:
## TODO: get better numbers our ssDNA model
elastic_modulus_times_area = 800 # pN http://markolab.bmbcb.northwestern.edu/marko/Cocco.CRP.02.pdf
d = 5*sep
if b1.type_.name[0] != b2.type_.name[0]:
""" Add a small extra distance to junction """
d += 3
k = conversion*elastic_modulus_times_area/d
# print(sep,d,k)
if b1 not in dists:
dists[b1] = dict()
if b2 not in dists:
dists[b2] = dict()
# dists[b1].append([b2,sep])
# dists[b2].append([b1,sep])
dists[b1][b2] = sep
dists[b2][b1] = sep
if b1 is b2: continue
# dists[[b1,b2]] = dists[[b2,b1]] = sep
bond = self.get_bond_potential(k,d)
parent.add_bond( b1, b2, bond, exclude=True )
# for s in self.segments:
# sepsum = 0
# beadsum = 0
# for b1 in s.beads:
# beadsum += b1.num_nt
# for bead_list in self._recursively_get_beads_within_bonds(b1, 1):
# assert(len(bead_list) == 1)
# if b1.idx < bead_list[-1].idx: # avoid double-counting
# for b2 in bead_list:
# if b2.parent == b1.parent:
# sepsum += dists[b1][b2]
# sepsum += sep
# print("Helix {}: bps {}, beads {}, separation {}".format(s.name, s.num_nt, beadsum, sepsum))
""" Add intrahelical angle potentials """
def get_effective_dsDNA_Lp(sep):
""" The persistence length of our model was found to be a
little off (probably due to NB interactions). This
attempts to compensate """
## For 1 bp, Lp=559, for 25 Lp = 524
beads_per_bp = sep/2
Lp0 = 147
# return 0.93457944*Lp0 ;# factor1
return 0.97*Lp0 ;# factor2
# factor = bead_per_bp * (0.954-0.8944
# return Lp0 * bead_per_bp
empirical_compensation_factor = max_basepairs_per_bead
if self.DEBUG: print("Adding intrahelical angle potentials")
for b1,b2,b3 in self._get_intrahelical_angle_beads():
## TODO: could be slightly smarter about sep
sep = 0.5*(0.5*b1.num_nt+b2.num_nt+0.5*b3.num_nt)
parent = self._getParent(b1,b2,b3)
kT = 0.58622522 # kcal/mol
if b1.type_.name[0] == "D" and b2.type_.name[0] == "D" and b3.type_.name[0] == "D":
Lp = get_effective_dsDNA_Lp(sep)
k = angle_spring_from_lp(sep,Lp)
if local_twist:
k_dihed = 0.25*k
k *= 0.75 # reduce because orientation beads impose similar springs
dihed = self.get_dihedral_potential(k_dihed,180)
parent.add_dihedral(b1,b2,b2.orientation_bead,b3, dihed)
elif b1.type_.name[0] == "S" and b2.type_.name[0] == "S" and b3.type_.name[0] == "S":
## TODO: get correct number from ssDNA model
k = angle_spring_from_lp(sep,2)
else:
## Considered as a sscrossover below
continue
angle = self.get_angle_potential(k,180)
parent.add_angle( b1, b2, b3, angle )
""" Add intrahelical exclusions """
if self.DEBUG: print("Adding intrahelical exclusions")
beads = dists.keys()
def _recursively_get_beads_within(b1,d,done=()):
ret = []
for b2,sep in dists[b1].items():
if b2 in done: continue
if sep < d:
ret.append( b2 )
done.append( b2 )
tmp = _recursively_get_beads_within(b2, d-sep, done)
if len(tmp) > 0: ret.extend(tmp)
return ret
exclusions = set()
for b1 in beads:
""" In addition to bond exclusiosn, only add exclusions
within like-type segments (i.e. dsDNA or ssDNA, not
junctions between the two) """
t = type(b1.parent)
if t is DoubleStrandedSegment:
cutoff = 20
elif t is SingleStrandedSegment:
cutoff = 5
else:
raise ValueError("Unexpected polymer segment type")
for b in _recursively_get_beads_within(b1, cutoff, done=[b1]):
if isinstance(b.parent,t):
exclusions.add((b1,b))
else:
break
# exclusions.update( tmp )
if self.DEBUG: print("Adding %d exclusions" % len(exclusions))
for b1,b2 in exclusions:
parent = self._getParent(b1,b2)
parent.add_exclusion( b1, b2 )
""" Twist potentials """
if local_twist:
if self.DEBUG: print("Adding twist potentials")
for b1 in beads:
if "orientation_bead" not in b1.__dict__: continue
for b2,sep in dists[b1].items():
if "orientation_bead" not in b2.__dict__: continue
if b2.idx < b1.idx: continue # Don't double-count
p1,p2 = [b.parent for b in (b1,b2)]
o1,o2 = [b.orientation_bead for b in (b1,b2)]
parent = self._getParent( b1, b2 )
""" Add heuristic 90 degree potential to keep orientation bead orthogonal """
Lp = get_effective_dsDNA_Lp(sep)
k = 0.5*angle_spring_from_lp(sep,Lp)
pot = self.get_angle_potential(k,90)
parent.add_angle(o1,b1,b2, pot)
parent.add_angle(b1,b2,o2, pot)
## TODO: improve this
twist_per_nt = 0.5 * (p1.twist_per_nt + p2.twist_per_nt)
angle = sep*twist_per_nt
if angle > 360 or angle < -360:
print("WARNING: twist angle out of normal range... proceeding anyway")
# raise Exception("The twist between beads is too large")
k = self._get_twist_spring_constant(sep)
if escapable_twist:
pot = self.get_dihedral_potential(k,angle,max_potential=1)
else:
pot = self.get_dihedral_potential(k,angle)
parent.add_dihedral(o1,b1,b2,o2, pot)
def k_angle(sep):
return 0.5*angle_spring_from_lp(sep,147)
def k_xover_angle(sep):
return 0.5 * k_angle(sep)
def add_local_crossover_strand_orientation_potential(b1,b2, b1_on_fwd_strand):
""" Adds a dihedral angle potential so bead b2 at opposite
end of crossover stays on correct side of helix of b1 """
u1 = b1.get_intrahelical_above(all_types=False)
d1 = b1.get_intrahelical_below(all_types=False)
sign = 1 if b1_on_fwd_strand else -1
# if b1.parent.name == "8-1" or b2.parent.name == "8-1":
# print()
# print(b1.parent.name, b2.parent.name, b1_on_fwd_strand)
# import pdb
# pdb.set_trace()
a,b,c = b2,b1,d1
if c is None or c is a:
c = u1
sign *= -1
if c is None or c is a: return
try:
d = b1.orientation_bead
except:
return
k = k_xover_angle(sep=1) # TODO
pot = self.get_dihedral_potential(k, sign*120)
self.add_dihedral( a,b,c,d, pot )
def add_local_tee_orientation_potential(b1,b2, b1_on_fwd_strand, b2_on_fwd_strand):
""" b1 is the end of a helix, b2 is in the middle This
adds a dihedral angle potential so helix of b1 is oriented
properly relative to strand on b2 """
u1,u2 = [b.get_intrahelical_above(all_types=False) for b in (b1,b2)]
d1,d2 = [b.get_intrahelical_below(all_types=False) for b in (b1,b2)]
angle = 150
if not b2_on_fwd_strand: angle -= 180
a,b,c = u2,b2,b1
if a is None:
a = d2
angle -= 180
try:
d = b1.orientation_bead
except:
d = None
angle -= 120
while angle > 180:
angle -= 360
while angle < -180:
angle += 360
k = k_xover_angle(sep=1) # TODO
if a is not None and d is not None:
pot = self.get_dihedral_potential(k,angle)
self.add_dihedral( a,b,c,d, pot )
## Add 180 degree angle potential
a,b,c = b2,b1,u1
if c is None: c = d1
if c is not None:
pot = self.get_angle_potential(0.5*k,180)
self.add_angle( a,b,c, pot )
def add_parallel_crossover_potential(b1,b2):
## Get beads above and below
u1,u2 = [b.get_intrahelical_above(all_types=False) for b in (b1,b2)]
d1,d2 = [b.get_intrahelical_below(all_types=False) for b in (b1,b2)]
dotProduct = b1.parent.contour_to_tangent(b1.contour_position).dot(
b2.parent.contour_to_tangent(b2.contour_position) )
if dotProduct < 0:
tmp = d2
d2 = u2
u2 = tmp
a = None
if u1 is not None and u2 is not None:
t0 = 0
a,b,c,d = (u1,b1,b2,u2)
elif d1 is not None and d2 is not None:
t0 = 0
a,b,c,d = (d1,b1,b2,d2 )
elif d1 is not None and u2 is not None:
t0 = 180
a,b,c,d = (d1,b1,b2,u2)
elif u1 is not None and d2 is not None:
t0 = 180
a,b,c,d = (u1,b1,b2,d2)
## TODO?: Check length-dependence of this potential
if a is not None:
k = k_xover_angle( dists[b][a]+dists[c][d] )
pot = self.get_dihedral_potential(k,t0)
self.add_dihedral( a,b,c,d, pot )
...
""" Functions for adding crossover potentials """
def add_ss_crossover_potentials(connection,A,B, add_bond=True):
b1,b2 = [loc.particle for loc in (A,B)]
if (b1,b2,A.on_fwd_strand,B.on_fwd_strand) in processed_crossovers:
return
processed_crossovers.add((b1,b2,A.on_fwd_strand,B.on_fwd_strand))
processed_crossovers.add((b2,b1,B.on_fwd_strand,A.on_fwd_strand))
if b1 is b2:
""" Catch attempts to add "crossover potentials" at
intrahelical junctions between ds and ssDNA """
if A.container is not b1.parent:
b1 = A.container.get_nearest_bead(A.address)
if B.container is not b2.parent:
b2 = B.container.get_nearest_bead(B.address)
if b1 is b2:
return
## TODO: improve parameters
if add_bond:
pot = self.get_bond_potential(4,12)
self.add_bond(b1,b2, pot)
## Add potentials to provide a sensible orientation
## TODO refine potentials against all-atom simulation data
if local_twist:
add_local_crossover_strand_orientation_potential(b1,b2, A.on_fwd_strand)
add_local_crossover_strand_orientation_potential(b2,b1, B.on_fwd_strand)
def add_crossover_potentials(connection,A,B):
## TODO: use a better description here
b1,b2 = [loc.particle for loc in (A,B)]
if (b1,b2,A.on_fwd_strand,B.on_fwd_strand) in processed_crossovers:
return
processed_crossovers.add((b1,b2,A.on_fwd_strand,B.on_fwd_strand))
processed_crossovers.add((b2,b1,B.on_fwd_strand,A.on_fwd_strand))
if b1 is b2:
""" Catch attempts to add "crossover potentials" at
intrahelical junctions between ds and ssDNA """
return
""" Add bond potential """
pot = self.get_bond_potential(4,18.5)
self.add_bond(b1,b2, pot)
""" Add parallel helices potential, possibly """
## Add potential to provide a particular orinetation
nt1,nt2 = [l.get_nt_pos() for l in (A,B)]
is_end1, is_end2 = [nt in (0,l.container.num_nt-1) for nt,l in zip((nt1,nt2),(A,B))]
is_T_junction = (is_end1 and not is_end2) or (is_end2 and not is_end1)
if (not is_end1) and (not is_end2):
## TODO?: Only apply this potential if not local_twist
add_parallel_crossover_potential(b1,b2)
# dotProduct = b1.parent.contour_to_tangent(b1.contour_position).dot(
# b2.parent.contour_to_tangent(b2.contour_position) )
if local_twist:
if is_T_junction:
""" Special case: one helix extends away from another in T-shaped junction """
if is_end1:
b1_forward = A.on_fwd_strand if nt1 == 0 else not A.on_fwd_strand
add_local_tee_orientation_potential(b1,b2, b1_forward, B.on_fwd_strand)
else:
add_local_crossover_strand_orientation_potential(b1,b2, A.on_fwd_strand)
if is_end2:
b2_forward = B.on_fwd_strand if nt2 == 0 else not B.on_fwd_strand
add_local_tee_orientation_potential(b2,b1, b2_forward, A.on_fwd_strand)
else:
add_local_crossover_strand_orientation_potential(b2,b1, B.on_fwd_strand)
else:
""" Normal case: add orientation potential """
add_local_crossover_strand_orientation_potential(b1,b2, A.on_fwd_strand)
add_local_crossover_strand_orientation_potential(b2,b1, B.on_fwd_strand)
""" Add connection potentials """
processed_crossovers = set()
# pdb.set_trace()
for c,A,B in self.get_connections("sscrossover"):
p1,p2 = [loc.container for loc in (A,B)]
assert(any([isinstance(p,SingleStrandedSegment) for p in (p1,p2)]))
add_ss_crossover_potentials(c,A,B)
for c,A,B in self.get_connections("intrahelical"):
ps = [loc.container for loc in (A,B)]
if any([isinstance(p,SingleStrandedSegment) for p in ps]) and \
any([isinstance(p,DoubleStrandedSegment) for p in ps]):
add_ss_crossover_potentials(c,A,B, add_bond=False)
for c,A,B in sum([self.get_connections(term) for term in ("crossover","terminal_crossover")],[]):
p1,p2 = [loc.container for loc in (A,B)]
if any([isinstance(p,SingleStrandedSegment) for p in (p1,p2)]):
add_ss_crossover_potentials(c,A,B)
else:
add_crossover_potentials(c,A,B)
## todotodo check that this works
for crossovers in self.get_consecutive_crossovers():
if local_twist: break
## filter crossovers
for i in range(len(crossovers)-2):
c1,A1,B1,dir1 = crossovers[i]
c2,A2,B2,dir2 = crossovers[i+1]
s1,s2 = [l.container for l in (A1,A2)]
sep = A1.particle.get_nt_position(s1,near_address=A1.address) - A2.particle.get_nt_position(s2,near_address=A2.address)
sep = np.abs(sep)
assert(sep >= 0)
n1,n2,n3,n4 = (B1.particle, A1.particle, A2.particle, B2.particle)
"""
<cos(q)> = exp(-s/Lp) = integrate( cos[x] exp(-A x^2), {x, 0, pi} ) / integrate( exp(-A x^2), {x, 0, pi} )
"""
## From http://www.annualreviews.org/doi/pdf/10.1146/annurev.bb.17.060188.001405
## units "3e-19 erg cm/ 295 k K" "nm" =~ 73
Lp = s1.twist_persistence_length/0.34 # set semi-arbitrarily as there is a large spread in literature
def get_spring(sep):
fitFun = lambda x: np.real(erf( (4*np.pi*x + 1j)/(2*np.sqrt(x)) )) * np.exp(-1/(4*x)) / erf(2*np.sqrt(x)*np.pi) - np.exp(-sep/Lp)
k = opt.leastsq( fitFun, x0=np.exp(-sep/Lp) )
return k[0][0] * 2*kT*0.00030461742
k = get_spring( max(sep,2) )
t0 = sep*s1.twist_per_nt # TODO weighted avg between s1 and s2
# pdb.set_trace()
if A1.on_fwd_strand: t0 -= 120
if dir1 != dir2:
A2_on_fwd = not A2.on_fwd_strand
else:
A2_on_fwd = A2.on_fwd_strand
if A2_on_fwd: t0 += 120
# t0 = (t0 % 360
# if n2.idx == 0:
# print( n1.idx,n2.idx,n3.idx,n4.idx,k,t0,sep )
# if sep == 0 and n1 is not n4:
if sep == 0:
# pot = self.get_angle_potential(k,t0)
# self.add_angle( n1,n2,n4, pot )
pass
else:
pot = self.get_dihedral_potential(k,t0)
self.add_dihedral( n1,n2,n3,n4, pot )
for callback in self._generate_bead_callbacks:
callback(self)
# ## remove duplicate potentials; ## TODO ensure that they aren't added twice in the first place?
# self.remove_duplicate_terms()
def walk_through_helices(segment, direction=1, processed_segments=None):
"""
First and last segment should be same for circular helices
"""
assert( direction in (1,-1) )
if processed_segments == None:
processed_segments = set()
def segment_is_new_helix(s):
return isinstance(s,DoubleStrandedSegment) and s not in processed_segments
new_s = None
s = segment
## iterate intrahelically connected dsDNA segments
while segment_is_new_helix(s):
conn_locs = s.get_contour_sorted_connections_and_locations("intrahelical")[::direction]
processed_segments.add(new_s)
new_s = None
new_dir = None
for i in range(len(conn_locs)):
c,A,B = conn_locs[i]
## TODO: handle change of direction
# TODOTODO
address = 1*(direction==-1)
if A.address == address and segment_is_new_helix(B.container):
new_s = B.container
assert(B.address in (0,1))
new_dir = 2*(B.address == 0) - 1
break
yield s,direction
s = new_s # will break if None
direction = new_dir
# if new_s is None:
# break
# else:
# s = new_s
# yield s
## return s
def get_consecutive_crossovers(self):
## TODOTODO TEST
crossovers = []
processed_segments = set()
for s1 in self.segments:
if not isinstance(s1,DoubleStrandedSegment):
continue
if s1 in processed_segments: continue
s0,d0 = list(SegmentModel.walk_through_helices(s1,direction=-1))[-1]
# s,direction = get_start_of_helices()
tmp = []
for s,d in SegmentModel.walk_through_helices(s0,-d0):
if s == s0 and len(tmp) > 0:
## end of circular helix, only add first crossover
cl_list = s.get_contour_sorted_connections_and_locations("crossover")
if len(cl_list) > 0:
tmp.append( cl_list[::d][0] + [d] )
else:
tmp.extend( [cl + [d] for cl in s.get_contour_sorted_connections_and_locations("crossover")[::d]] )
processed_segments.add(s)
crossovers.append(tmp)
return crossovers
def set_sequence(self, sequence, force=True):
if force:
self.strands[0].set_sequence(sequence)
else:
try:
self.strands[0].set_sequence(sequence)
except:
...
for s in self.segments:
s.randomize_unset_sequence()
def _generate_strands(self):
## clear strands
try:
for s in self.strands:
self.children.remove(s)
for seg in self.segments:
for d in ('fwd','rev'):
seg.strand_pieces[d] = []
except:
pass
self.strands = strands = []
""" Ensure unconnected ends have 5prime Location objects """
for seg in self.segments:
## TODO move into Segment calls
five_prime_locs = sum([seg.get_locations(s) for s in ("5prime","crossover","terminal_crossover")],[])
three_prime_locs = sum([seg.get_locations(s) for s in ("3prime","crossover","terminal_crossover")],[])
def is_start_5prime(l):
return l.get_nt_pos() < 1 and l.on_fwd_strand
def is_end_5prime(l):
return l.get_nt_pos() > seg.num_nt-2 and not l.on_fwd_strand
def is_start_3prime(l):
return l.get_nt_pos() < 1 and not l.on_fwd_strand
def is_end_3prime(l):
return l.get_nt_pos() > seg.num_nt-2 and l.on_fwd_strand
if seg.start5.connection is None:
if len(list(filter( is_start_5prime, five_prime_locs ))) == 0:
seg.add_5prime(0) # TODO ensure this is the same place
if 'end5' in seg.__dict__ and seg.end5.connection is None:
if len(list(filter( is_end_5prime, five_prime_locs ))) == 0:
seg.add_5prime(seg.num_nt-1,on_fwd_strand=False)
if 'start3' in seg.__dict__ and seg.start3.connection is None:
if len(list(filter( is_start_3prime, three_prime_locs ))) == 0:
seg.add_3prime(0,on_fwd_strand=False)
if seg.end3.connection is None:
if len(list(filter( is_end_3prime, three_prime_locs ))) == 0:
seg.add_3prime(seg.num_nt-1)
# print( [(l,l.get_connected_location()) for l in seg.locations] )
# addresses = np.array([l.address for l in seg.get_locations("5prime")])
# if not np.any( addresses == 0 ):
# ## check if end is connected
# for c,l,B in self.get_connections_and_locations():
# if c[0]
""" Build strands from connectivity of helices """
def _recursively_build_strand(strand, segment, pos, is_fwd, mycounter=0, move_at_least=0.5):
seg = segment
history = []
while True:
mycounter+=1
if mycounter > 10000:
raise Exception("Too many iterations")
#if seg.name == "22-1" and pos > 140:
# if seg.name == "22-2":
# import pdb
# pdb.set_trace()
end_pos, next_seg, next_pos, next_dir, move_at_least = seg.get_strand_segment(pos, is_fwd, move_at_least)
history.append((seg,pos,end_pos,is_fwd))
try:
strand.add_dna(seg, pos, end_pos, is_fwd)
except CircularDnaError:
## Circular DNA was found
break
except:
print("Unexpected error:", sys.exc_info()[0])
# import pdb
# pdb.set_trace()
# seg.get_strand_segment(pos, is_fwd, move_at_least)
# strand.add_dna(seg, pos, end_pos, is_fwd)
raise
if next_seg is None:
break
else:
seg,pos,is_fwd = (next_seg, next_pos, next_dir)
strand.history = list(history)
return history
strand_counter = 0
history = []
for seg in self.segments:
locs = filter(lambda l: l.connection is None, seg.get_5prime_locations())
if locs is None: continue
# for pos, is_fwd in locs:
for l in locs:
# print("Tracing",l)
# TODOTODO
pos = seg.contour_to_nt_pos(l.address, round_nt=True)
is_fwd = l.on_fwd_strand
s = Strand(segname="S{:03d}".format(len(strands)))
strand_history = _recursively_build_strand(s, seg, pos, is_fwd)
history.append((l,strand_history))
# print("{} {}".format(seg.name,s.num_nt))
strands.append(s)
## Trace circular DNA
def strands_cover_segment(segment, is_fwd=True):
direction = 'fwd' if is_fwd else 'rev'
nt = 0
for sp in segment.strand_pieces[direction]:
nt += sp.num_nt
return nt == segment.num_nt
def find_nt_not_in_strand(segment, is_fwd=True):
fwd_str = 'fwd' if is_fwd else 'rev'
def check(val):
assert(val >= 0 and val < segment.num_nt)
# print("find_nt_not_in_strand({},{}) returning {}".format(
# segment, is_fwd, val))
return val
if is_fwd:
last = -1
for sp in segment.strand_pieces[fwd_str]:
if sp.start-last > 1:
return check(last+1)
last = sp.end
return check(last+1)
else:
last = segment.num_nt
for sp in segment.strand_pieces[fwd_str]:
if last-sp.end > 1:
return check(last-1)
last = sp.start
return check(last-1)
def add_strand_if_needed(seg,is_fwd):
history = []
if not strands_cover_segment(seg, is_fwd):
pos = nt = find_nt_not_in_strand(seg, is_fwd)
s = Strand(is_circular = True)
history = _recursively_build_strand(s, seg, pos, is_fwd)
strands.append(s)
return history
for seg in self.segments:
add_strand_if_needed(seg,True)
if isinstance(seg, DoubleStrandedSegment):
add_strand_if_needed(seg,False)
self.strands = sorted(strands, key=lambda s:s.num_nt)[::-1]
def check_strands():
dsdna = filter(lambda s: isinstance(s,DoubleStrandedSegment), self.segments)
for s in dsdna:
nt_fwd = nt_rev = 0
for sp in s.strand_pieces['fwd']:
nt_fwd += sp.num_nt
for sp in s.strand_pieces['rev']:
nt_rev += sp.num_nt
assert( nt_fwd == s.num_nt and nt_rev == s.num_nt )
# print("{}: {},{} (fwd,rev)".format(s.name, nt_fwd/s.num_nt,nt_rev/s.num_nt))
check_strands()
## relabel segname
counter = 0
for s in self.strands:
if s.segname is None:
s.segname = "D%03d" % counter
counter += 1
def _assign_basepairs(self):
## Assign basepairs
for seg in self.segments:
if isinstance(seg, DoubleStrandedSegment):
strands1 = seg.strand_pieces['fwd'] # already sorted
strands2 = seg.strand_pieces['rev']
nts1 = [nt for s in strands1 for nt in s.children]
nts2 = [nt for s in strands2 for nt in s.children[::-1]]
assert(len(nts1) == len(nts2))
for nt1,nt2 in zip(nts1,nts2):
## TODO weakref
nt1.basepair = nt2
nt2.basepair = nt1
def write_atomic_ENM(self, output_name, lattice_type=None):
## TODO: ensure atomic model was generated already
if lattice_type is None:
try:
lattice_type = self.lattice_type
except:
lattice_type = "square"
else:
try:
if lattice_type != self.lattice_type:
print("WARNING: printing ENM with a lattice type ({}) that differs from model's lattice type ({})".format(lattice_type,self.lattice_type))
except:
pass
if lattice_type == "square":
enmTemplate = enmTemplateSQ
elif lattice_type == "honeycomb":
enmTemplate = enmTemplateHC
else:
raise Exception("Lattice type '%s' not supported" % self.latticeType)
## TODO: allow ENM to be created without first building atomic model
noStackPrime = 0
noBasepair = 0
with open("%s.exb" % output_name,'w') as fh:
# natoms=0
for seg in self.segments:
## Continue unless dsDNA
if not isinstance(seg,DoubleStrandedSegment): continue
for strand_piece in seg.strand_pieces['fwd'] + seg.strand_pieces['rev']:
for nt1 in strand_piece.children:
other = []
nt2 = nt1.basepair
if strand_piece.is_fwd:
other.append((nt2,'pair'))
nt2 = nt2.get_intrahelical_above()
if nt2 is not None and strand_piece.is_fwd:
## TODO: check if this already exists
other.append((nt2,'paircross'))
nt2 = nt1.get_intrahelical_above()
if nt2 is not None:
other.append((nt2,'stack'))
nt2 = nt2.basepair
if nt2 is not None and strand_piece.is_fwd:
other.append((nt2,'cross'))
for nt2,key in other:
"""
if np.linalg.norm(nt2.position-nt1.position) > 7:
import pdb
pdb.set_trace()
"""
key = ','.join((key,nt1.sequence[0],nt2.sequence[0]))
for n1, n2, d in enmTemplate[key]:
d = float(d)
k = 0.1
if lattice_type == 'honeycomb':
correctionKey = ','.join((key,n1,n2))
assert(correctionKey in enmCorrectionsHC)
dk,dr = enmCorrectionsHC[correctionKey]
k = float(dk)
d += float(dr)
i = nt1._get_atomic_index(name=n1)
j = nt2._get_atomic_index(name=n2)
fh.write("bond %d %d %f %.2f\n" % (i,j,k,d))
# print("NO STACKS found for:", noStackPrime)
# print("NO BASEPAIRS found for:", noBasepair)
## Loop dsDNA regions
push_bonds = []
processed_segs = set()
## TODO possibly merge some of this code with SegmentModel.get_consecutive_crossovers()
for segI in self.segments: # TODOTODO: generalize through some abstract intrahelical interface that effectively joins "segments", for now interhelical bonds that cross intrahelically-connected segments are ignored
if not isinstance(segI,DoubleStrandedSegment): continue
## Loop over dsDNA regions connected by crossovers
conn_locs = segI.get_contour_sorted_connections_and_locations("crossover")
other_segs = list(set([B.container for c,A,B in conn_locs]))
for segJ in other_segs:
if (segI,segJ) in processed_segs:
continue
processed_segs.add((segI,segJ))
processed_segs.add((segJ,segI))
## TODO perhaps handle ends that are not between crossovers
## Loop over ordered pairs of crossovers between the two
cls = filter(lambda x: x[-1].container == segJ, conn_locs)
cls = sorted( cls, key=lambda x: x[1].get_nt_pos() )
for cl1,cl2 in zip(cls[:-1],cls[1:]):
c1,A1,B1 = cl1
c2,A2,B2 = cl2
ntsI1,ntsI2 = [segI.contour_to_nt_pos(A.address) for A in (A1,A2)]
ntsJ1,ntsJ2 = [segJ.contour_to_nt_pos(B.address) for B in (B1,B2)]
ntsI = ntsI2-ntsI1+1
ntsJ = ntsJ2-ntsJ1+1
assert( np.isclose( ntsI, int(round(ntsI)) ) )
assert( np.isclose( ntsJ, int(round(ntsJ)) ) )
ntsI,ntsJ = [int(round(i)) for i in (ntsI,ntsJ)]
## Find if dsDNA "segments" are pointing in same direction
## could move this block out of the loop
tangentA = segI.contour_to_tangent(A1.address)
tangentB = segJ.contour_to_tangent(B1.address)
dot1 = tangentA.dot(tangentB)
tangentA = segI.contour_to_tangent(A2.address)
tangentB = segJ.contour_to_tangent(B2.address)
dot2 = tangentA.dot(tangentB)
if dot1 > 0.5 and dot2 > 0.5:
...
elif dot1 < -0.5 and dot2 < -0.5:
## TODO, reverse
...
# print("Warning: {} and {} are on antiparallel helices (not yet implemented)... skipping".format(A1,B1))
continue
else:
# print("Warning: {} and {} are on helices that do not point in similar direction... skipping".format(A1,B1))
continue
## Go through each nucleotide between the two
for ijmin in range(min(ntsI,ntsJ)):
i=j=ijmin
if ntsI < ntsJ:
j = int(round(float(ntsJ*i)/ntsI))
elif ntsJ < ntsI:
i = int(round(float(ntsI*j)/ntsJ))
ntI_idx = int(round(ntsI1+i))
ntJ_idx = int(round(ntsJ1+j))
## Skip nucleotides that are too close to crossovers
if i < 11 or j < 11: continue
if ntsI2-ntI_idx < 11 or ntsJ2-ntJ_idx < 11: continue
## Find phosphates at ntI/ntJ
for direction in [True,False]:
try:
i = segI._get_atomic_nucleotide(ntI_idx, direction)._get_atomic_index(name="P")
j = segJ._get_atomic_nucleotide(ntJ_idx, direction)._get_atomic_index(name="P")
push_bonds.append((i,j))
except:
# print("WARNING: could not find 'P' atom in {}:{} or {}:{}".format( segI, ntI_idx, segJ, ntJ_idx ))
...
# print("PUSH BONDS:", len(push_bonds))
if not self.useTclForces:
with open("%s.exb" % output_name, 'a') as fh:
for i,j in push_bonds:
fh.write("bond %d %d %f %.2f\n" % (i,j,1.0,31))
else:
flat_push_bonds = list(sum(push_bonds))
atomList = list(set( flat_push_bonds ))
with open("%s.forces.tcl" % output_name,'w') as fh:
fh.write("set atomList {%s}\n\n" %
" ".join([str(x-1) for x in atomList]) )
fh.write("set bonds {%s}\n" %
" ".join([str(x-1) for x in flat_push_bonds]) )
fh.write("""
foreach atom $atomList {
addatom $atom
}
proc calcforces {} {
global atomList bonds
loadcoords rv
foreach i $atomList {
set force($i) {0 0 0}
}
foreach {i j} $bonds {
set rvec [vecsub $rv($j) $rv($i)]
# lassign $rvec x y z
# set r [expr {sqrt($x*$x+$y*$y+$z*$z)}]
set r [getbond $rv($j) $rv($i)]
set f [expr {2*($r-31.0)/$r}]
vecadd $force($i) [vecscale $f $rvec]
vecadd $force($j) [vecscale [expr {-1.0*$f}] $rvec]
}
foreach i $atomList {
addforce $i $force($i)
}
}
""")
def dimensions_from_structure( self, padding_factor=1.5, isotropic=False ):
positions = []
for s in self.segments:
positions.append(s.contour_to_position(0))
positions.append(s.contour_to_position(0.5))
positions.append(s.contour_to_position(1))
positions = np.array(positions)
dx,dy,dz = [(np.max(positions[:,i])-np.min(positions[:,i])+30)*padding_factor for i in range(3)]
if isotropic:
dx = dy = dz = max((dx,dy,dz))
return [dx,dy,dz]
def add_grid_potential(self, grid_file, scale=1, per_nucleotide=True):
grid_file = Path(grid_file)
if not grid_file.is_file():
raise ValueError("Grid file {} does not exist".format(grid_file))
if not grid_file.is_absolute():
grid_file = Path.cwd() / grid_file
self.grid_potentials.append((grid_file,scale,per_nucleotide))
def _apply_grid_potentials_to_beads(self, bead_type_dict):
if len(self.grid_potentials) > 1:
raise NotImplementedError("Multiple grid potentials are not yet supported")
for grid_file, scale, per_nucleotide in self.grid_potentials:
for key,particle_type in bead_type_dict.items():
if particle_type.name[0] == "O": continue
s = scale*particle_type.nts if per_nucleotide else scale
try:
particle_type.grid = particle_type.grid + (grid_file, s)
except:
particle_type.grid = tuple((grid_file, s))
def _generate_atomic_model(self, scale=1):
## TODO: deprecate
self.generate_atomic_model(scale=scale)
def generate_atomic_model(self, scale=1):
self.clear_beads()
self.children = self.strands # TODO: is this going to be okay? probably
first_atomic_index = 0
for s in self.strands:
first_atomic_index = s.generate_atomic_model(scale,first_atomic_index)
self._assign_basepairs()
def generate_oxdna_model(self, scale=1):
self.clear_beads()
self.children = self.strands
for s in self.strands:
s.generate_oxdna_model()
def vmd_tube_tcl(self, file_name="drawTubes.tcl"):
with open(file_name, 'w') as tclFile:
tclFile.write("## beginning TCL script \n")
def draw_tube(segment,radius_value=10, color="cyan", resolution=5):
tclFile.write("## Tube being drawn... \n")
contours = np.linspace(0,1, max(2,1+segment.num_nt//resolution) )
rs = [segment.contour_to_position(c) for c in contours]
radius_value = str(radius_value)
tclFile.write("graphics top color {} \n".format(str(color)))
for i in range(len(rs)-2):
r0 = rs[i]
r1 = rs[i+1]
filled = "yes" if i in (0,len(rs)-2) else "no"
tclFile.write("graphics top cylinder {{ {} {} {} }} {{ {} {} {} }} radius {} resolution 30 filled {} \n".format(r0[0], r0[1], r0[2], r1[0], r1[1], r1[2], str(radius_value), filled))
tclFile.write("graphics top sphere {{ {} {} {} }} radius {} resolution 30\n".format(r1[0], r1[1], r1[2], str(radius_value)))
r0 = rs[-2]
r0 = rs[-1]
tclFile.write("graphics top cylinder {{ {} {} {} }} {{ {} {} {} }} radius {} resolution 30 filled yes \n".format(r0[0], r0[1], r0[2], r1[0], r1[1], r1[2], str(radius_value)))
## material
tclFile.write("graphics top materials on \n")
tclFile.write("graphics top material AOEdgy \n")
## iterate through the model segments
for s in self.segments:
if isinstance(s,DoubleStrandedSegment):
tclFile.write("## dsDNA! \n")
draw_tube(s,10,"cyan")
elif isinstance(s,SingleStrandedSegment):
tclFile.write("## ssDNA! \n")
draw_tube(s,3,"orange",resolution=1.5)
else:
raise Exception ("your model includes beads that are neither ssDNA nor dsDNA")
## tclFile complete
tclFile.close()
def vmd_cylinder_tcl(self, file_name="drawCylinders.tcl"):
#raise NotImplementedError
with open(file_name, 'w') as tclFile:
tclFile.write("## beginning TCL script \n")
def draw_cylinder(segment,radius_value=10,color="cyan"):
tclFile.write("## cylinder being drawn... \n")
r0 = segment.contour_to_position(0)
r1 = segment.contour_to_position(1)
radius_value = str(radius_value)
color = str(color)
tclFile.write("graphics top color {} \n".format(color))
tclFile.write("graphics top cylinder {{ {} {} {} }} {{ {} {} {} }} radius {} resolution 30 filled yes \n".format(r0[0], r0[1], r0[2], r1[0], r1[1], r1[2], radius_value))
## material
tclFile.write("graphics top materials on \n")
tclFile.write("graphics top material AOEdgy \n")
## iterate through the model segments
for s in self.segments:
if isinstance(s,DoubleStrandedSegment):
tclFile.write("## dsDNA! \n")
draw_cylinder(s,10,"cyan")
elif isinstance(s,SingleStrandedSegment):
tclFile.write("## ssDNA! \n")
draw_cylinder(s,3,"orange")
else:
raise Exception ("your model includes beads that are neither ssDNA nor dsDNA")
## tclFile complete
tclFile.close()