segmentmodel.py 41.6 KB
Newer Older
1
2
import numpy as np
from arbdmodel import PointParticle, ParticleType, Group, ArbdModel
3
from coords import rotationAboutAxis, quaternion_from_matrix, quaternion_to_matrix
4
5
6
7
from nonbonded import *
from copy import copy, deepcopy
from nbPot import nbDnaScheme

cmaffeo2's avatar
cmaffeo2 committed
8
9
from scipy.special import erf
import scipy.optimize as opt
10
from scipy import interpolate
cmaffeo2's avatar
cmaffeo2 committed
11

12
import types
13
import pdb
14
"""
cmaffeo2's avatar
cmaffeo2 committed
15
16
TODO:
 - document
17
18
19
20
21
22
23
 - handle crossovers
    - connections in the middle of a segment?
    - merge beads at ends of connected helices?
 - map to atomic representation
 - remove performance bottlenecks
 - test for large systems
 - assign sequence
24
25
26
27
28
"""

class Location():
    """ Site for connection within an object """
    def __init__(self, container, address, type_):
29
        ## TODO: remove cyclic references(?)
30
        self.container = container
31
        self.address = address  # represents position along contour length in segments
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
        self.type_ = type_
        self.particle = None

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_
        
# class ConnectableElement(Transformable):
class ConnectableElement():
    """ Abstract base class """
    def __init__(self, connections=[]):
        self.connections = connections

cmaffeo2's avatar
cmaffeo2 committed
50
    def get_connections_and_locations(self, type_=None, exclude=[]):
51
52
53
54
        """ Returns a list with each entry of the form:
            connection, location_in_self, location_in_other """
        ret = []
        for c in self.connections:
cmaffeo2's avatar
cmaffeo2 committed
55
            if type_ is None or c.type_ == type_ and type_ not in exclude:
56
                if   c.A.container is self:
57
                    ret.append( [c, c.A, c.B] )
58
                elif c.B.container is self:
59
60
61
62
63
                    ret.append( [c, c.B, c.A] )
                else:
                    raise Exception("Object contains connection that fails to refer to object")
        return ret

64
65
66
    def _connect(self, other, connection):
        self.connections.append(connection)
        other.connections.append(connection)
67
68
    # def _find_connections(self, loc):
    #     return [c for c in self.connections if c.A == loc or c.B == loc]
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98

class SegmentParticle(PointParticle):
    def __init__(self, type_, position, name="A", segname="A", **kwargs):
        self.contour_position = None
        PointParticle.__init__(self, type_, position, name=name, segname=segname, **kwargs)
        self.intrahelical_neighbors = []
        self.other_neighbors = []

    def get_contour_position(self,seg):
        assert( isinstance(seg,Segment) )
        if seg == self.parent:
            return self.contour_position
        else:
            for c,A,B in self.parent.get_connections_and_locations():
                if A.particle is self and B.container is seg:
                    nt = np.abs( (self.contour_position - A.address)*A.container.num_nts )
                    if B.address < 0.5:
                        return B.address-nt/seg.num_nts
                    else:
                        return B.address+nt/seg.num_nts
            print("")
            for c,A,B in self.parent.get_connections_and_locations():
                print("  ",c.type_)
                print(A,B)
                print(A.particle,self)
                print(B.container,seg)
            print("")
            import pdb
            pdb.set_trace()
            raise Exception("Did not find location for particle {} in Segment {}".format(self,seg))
99
100
101
102
103
104
105
106
107
108
109
110
       
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,                 
                              )
cmaffeo2's avatar
cmaffeo2 committed
111
112
113
114
115
    orientation_particle = ParticleType("O",
                                        diffusivity = 100,
                                        mass = 300,
                                        radius = 1,
                                    )
116

cmaffeo2's avatar
cmaffeo2 committed
117
    # orientation_bond = HarmonicBond(10,2)
118
    orientation_bond = HarmonicBond(30,1.5, rRange = (0,500) )
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133

    ssDNA_particle = ParticleType("S",
                                  diffusivity = 43.5,
                                  mass = 150,
                                  radius = 3,                 
                              )

    def __init__(self, name, num_nts, 
                 start_position = np.array((0,0,0)),
                 end_position = None, 
                 segment_model = None):

        Group.__init__(self, name, children=[])
        ConnectableElement.__init__(self, connections=[])

cmaffeo2's avatar
cmaffeo2 committed
134
135
136
137
138
        self.start_orientation = None
        self.twist_per_nt = 0

        self.beads = [c for c in self.children] # self.beads will not contain orientation beads

139
140
141
        self._bead_model_generation = 0    # TODO: remove?
        self.segment_model = segment_model # TODO: remove?

cmaffeo2's avatar
cmaffeo2 committed
142
        self.num_nts = int(num_nts)
143
144
145
146
147
        if end_position is None:
            end_position = np.array((0,0,self.distance_per_nt*num_nts)) + start_position
        self.start_position = start_position
        self.end_position = end_position

148
149
150
151
152
        ## Set up interpolation for positions
        a = np.array([self.start_position,self.end_position]).T
        tck, u = interpolate.splprep( a, u=[0,1], s=0, k=1)
        self.position_spline_params = tck

153
154
155
156
157
    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
158
159
160
161
162
163
164
165

    def contour_to_position(self,s):
        p = interpolate.splev( s, self.position_spline_params )
        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, der=1 )
166
167
        t = (t / np.linalg.norm(t,axis=0))
        return t.T
168
169
170
171
172
173
174
        

    def contour_to_orientation(self,s):
        if self.start_orientation is not None:
            # axis = self.start_orientation.dot( np.array((0,0,1)) )
            if self.quaternion_spline_params is None:
                axis = self.contour_to_tangent(s)
175
                orientation = rotationAboutAxis( axis, s*self.twist_per_nt*self.num_nts, normalizeAxis=True )
176
177
178
179
180
181
182
183
184
185
186
                ## TODO: ensure this is correct
                # orientation = self.start_orientation.dot(orientation) # .dot( self.start_orientation )
                orientation = orientation.dot( self.start_orientation )
            else:
                q = interpolate.splev(s, self.quaternion_spline_params)
                orientation = quaternion_to_matrix(q)
        else:
            orientation = None
        return orientation


cmaffeo2's avatar
cmaffeo2 committed
187
188
189
    def _get_num_beads(self, max_basepairs_per_bead, max_nucleotides_per_bead ):
        raise NotImplementedError

190
    def _generate_one_bead(self, contour_position, nts):
191
192
193
194
195
196
197
        raise NotImplementedError

    def _assign_particles_to_locations(self):
        raise NotImplementedError

    def get_all_consecutive_beads(self, number):
        assert(number >= 1)
cmaffeo2's avatar
cmaffeo2 committed
198
        ## Assume that consecutive beads in self.beads are bonded
199
        ret = []
cmaffeo2's avatar
cmaffeo2 committed
200
201
        for i in range(len(self.beads)-number+1):
            tmp = [self.beads[i+j] for j in range(0,number)]
202
            ret.append( tmp )
203
        return ret   
204

205
206
207
    def _add_bead(self,b,set_contour=False):
        if set_contour:
            b.contour_position = b.get_contour_position(self)
208
        
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
        # assert(b.parent is None)
        if b.parent is not None:
            b.parent.children.remove(b)
        b.parent = self
        self.children.append(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)
            o.parent = self
            self.children.append(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 = []
        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)
        assert(len(old_children) == len(self.children))
        assert(len(old_beads) == len(self.beads))
237

cmaffeo2's avatar
cmaffeo2 committed
238
    def _generate_beads(self, bead_model, max_basepairs_per_bead, max_nucleotides_per_bead):
239
240
        
        """ Generate beads (positions, types, etcl) and bonds, angles, dihedrals, exclusions """
cmaffeo2's avatar
cmaffeo2 committed
241
        ## TODO: decide whether to remove bead_model argument
242
        ##       (currently unused)
cmaffeo2's avatar
cmaffeo2 committed
243

244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
        ## First find points between-which beads must be generated
        locs = sorted([loc for c,loc,other_loc in self.get_connections_and_locations()], key=lambda l:l.address)
        existing_beads = [l.particle for l in locs if l.particle is not None]
        for b in existing_beads:
            assert(b.parent is not None)

        ## Add ends if they don't exist yet
        ## TODO: what about 1 nt segments?
        if len(existing_beads) == 0 or existing_beads[0].get_contour_position(self) > 0:
            b = self._generate_one_bead(0, 0)
            existing_beads = [b] + existing_beads
        if existing_beads[-1].get_contour_position(self) < 1:
            b = self._generate_one_bead(1, 0)
            existing_beads.append(b)
        assert(len(existing_beads) > 1)

        ## Walk through existing_beads, add beads between
        tmp_children = []       # build list of children in nice order
262
        last = None
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
        for I in range(len(existing_beads)-1):
            eb1,eb2 = [existing_beads[i] for i in (I,I+1)]

            # print(" %s working on %d to %d" % (self.name, eb1.position[2], eb2.position[2]))
            e_ds = eb2.get_contour_position(self) - eb1.get_contour_position(self)
            num_beads = self._get_num_beads( e_ds, max_basepairs_per_bead, max_nucleotides_per_bead )
            ds = e_ds / (num_beads+1)
            nts = ds*self.num_nts
            eb1.num_nts += 0.5*nts
            eb2.num_nts += 0.5*nts

            ## Add beads
            if eb1.parent == self:
                tmp_children.append(eb1)

            s0 = eb1.get_contour_position(self)
            if last is not None:
                last.intrahelical_neighbors.append(eb1)
                eb1.intrahelical_neighbors.append(last)
            last = eb1
            for j in range(num_beads):
                s = ds*(j+1) + s0
                b = self._generate_one_bead(s,nts)

                last.intrahelical_neighbors.append(b)
                b.intrahelical_neighbors.append(last)
                last = b
                tmp_children.append(b)

        last.intrahelical_neighbors.append(eb2)
        eb2.intrahelical_neighbors.append(last)

        if eb2.parent == self:
            tmp_children.append(eb2)
        self._rebuild_children(tmp_children)
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313

    def _regenerate_beads(self, max_nts_per_bead=4, ):
        ...

    def _generate_atomic(self, atomic_model):
        ...
    

class DoubleStrandedSegment(Segment):

    """ Class that describes a segment of ssDNA. When built from
    cadnano models, should not span helices """

    def __init__(self, name, num_nts, start_position = np.array((0,0,0)),
                 end_position = None, 
                 segment_model = None,
cmaffeo2's avatar
cmaffeo2 committed
314
315
                 local_twist = False,
                 num_turns = None,
316
                 start_orientation = None):
cmaffeo2's avatar
cmaffeo2 committed
317
318
319
        
        self.helical_rise = 10.44
        self.distance_per_nt = 3.4
320
321
322
323
324
        Segment.__init__(self, name, num_nts, 
                         start_position,
                         end_position, 
                         segment_model)

cmaffeo2's avatar
cmaffeo2 committed
325
326
327
328
329
330
331
332
333
        self.local_twist = local_twist
        if num_turns is None:
            num_turns = float(num_nts) / self.helical_rise
        self.twist_per_nt = float(360 * num_turns) / num_nts

        if start_orientation is None:
            start_orientation = np.array(((1,0,0),(0,1,0),(0,0,1)))
        self.start_orientation = start_orientation

334
335
        self.nicks = []

336
        self.start = self.start5 = Location( self, address=0, type_= "end5" )
337
338
        self.start3 = Location( self, address=0, type_ = "end3" )

339
340
        self.end = self.end5 = Location( self, address=1, type_= "end5" )
        self.end3 = Location( self, address=1, type_ = "end3" )
341

342
343
344
345
346
347
348
349
350
        ## Set up interpolation for azimuthal angles 
        a = np.array([self.start_position,self.end_position]).T
        tck, u = interpolate.splprep( a, u=[0,1], s=0, k=1)
        self.position_spline_params = tck
        
        ## TODO: initialize sensible spline for orientation
        self.quaternion_spline_params = None


351
    ## Convenience methods
352
    ## TODO: add errors if incorrect connections are made
353
    def connect_start5(self, end3, type_="intrahelical", force_connection=False):
354
355
        if isinstance(end3, SingleStrandedSegment):
            end3 = end3.end3
356
357
        self._connect_ends( self.start5, end3, type_, force_connection = force_connection )
    def connect_start3(self, end5, type_="intrahelical", force_connection=False):
358
359
        if isinstance(end5, SingleStrandedSegment):
            end5 = end5.end5
360
361
        self._connect_ends( self.start3, end5, type_, force_connection = force_connection )
    def connect_end3(self, end5, type_="intrahelical", force_connection=False):
362
363
        if isinstance(end5, SingleStrandedSegment):
            end5 = end5.end5
364
365
        self._connect_ends( self.end3, end5, type_, force_connection = force_connection )
    def connect_end5(self, end3, type_="intrahelical", force_connection=False):
366
367
        if isinstance(end3, SingleStrandedSegment):
            end3 = end3.end3
368
        self._connect_ends( self.end5, end3, type_, force_connection = force_connection )
369

cmaffeo2's avatar
cmaffeo2 committed
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
    def crossover(self, nt, other, other_nt, strands=None, other_strands=None):
        """ Add a crossover between two helices """
        ## Validate other, nt, other_nt
        ##   TODO

        ## Fix input
        if strands is None and other_strands is None:
            ## Regular double crossover
            strands = ['fwd','rev']
            other_strands = list(strands[::-1])
        elif strands is None:
            strands = []
            for d in other_strands:
                if d == 'fwd': strands.append('rev')
                elif d == 'rev': strands.append('fwd')
        elif other_strands == None:
            other_strands = []
            for d in strands:
                if d == 'fwd': other_strands.append('rev')
                elif d == 'rev': other_strands.append('fwd')

        if isinstance(strands,str):
            strands = [strands]
        if isinstance(other_strands,str):
            other_strands = [other_strands]

        ## Create locations, connections and add to segments
        c = nt/self.num_nts
        print(self.name,nt,c)
        assert(c >= 0 and c <= 1)
        loc = Location( self, address=c, type_ = strands )

        c = other_nt/other.num_nts
        print(other.name,other_nt,c)
        assert(c >= 0 and c <= 1)
        other_loc = Location( other, address=c, type_ = other_strands )
        self._connect(other, Connection( loc, other_loc, type_="crossover" )) # TODO: use multiple crossover types

408
    ## Real work
409
    def _connect_ends(self, end1, end2, type_, force_connection):
410
        ## TODO remove self?
411
412
413
414
415
        ## validate the input
        for end in (end1, end2):
            assert( isinstance(end, Location) )
            assert( end.type_ in ("end3","end5") )
        assert( end1.type_ != end2.type_ )
416
        ## Create and add connection
417
        end1.container._connect( end2.container, Connection( end1, end2, type_=type_ ) )
418

419
420
    def _get_num_beads(self, contour, max_basepairs_per_bead, max_nucleotides_per_bead):
        return int(contour*self.num_nts // max_basepairs_per_bead)
cmaffeo2's avatar
cmaffeo2 committed
421

422
423
    def _generate_one_bead(self, contour_position, nts):
        pos = self.contour_to_position(contour_position)
cmaffeo2's avatar
cmaffeo2 committed
424
        if self.local_twist:
425
            orientation = self.contour_to_orientation(contour_position)
cmaffeo2's avatar
cmaffeo2 committed
426
            opos = pos + orientation.dot( np.array((Segment.orientation_bond.r0,0,0)) )
427
428
429
430
431
432
            o = SegmentParticle( Segment.orientation_particle, opos, nts,
                                 num_nts=nts, parent=self )
            bead = SegmentParticle( Segment.dsDNA_particle, pos, nts,
                                    num_nts=nts, parent=self, 
                                    orientation_bead=o,
                                    contour_position=contour_position )
cmaffeo2's avatar
cmaffeo2 committed
433
434

        else:
435
436
437
438
            bead = SegmentParticle( Segment.dsDNA_particle, pos, nts,
                                    num_nts=nts, parent=self,
                                    contour_position=contour_position )
        self._add_bead(bead)
cmaffeo2's avatar
cmaffeo2 committed
439
440
        return bead

441

442

443
    def _assign_particles_to_locations(self):
444
445
446
447
448
449
450
451
        if self.start5.particle is None:
            assert(self.beads[0].parent is not None)
            self.start5.particle = self.beads[0]
        if self.end3.particle is None:
            assert(self.beads[-1].parent is not None)
            self.end3.particle = self.beads[-1]
        self.start3.particle =  self.start5.particle 
        self.end5.particle   =  self.end3.particle
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492

    def _generate_atomic(self, atomic_model):
        ...
    
        
    # def add_crossover(self, locationInA, B, locationInB):
    #     j = Crossover( [self, B], [locationInA, locationInB] )
    #     self._join(B,j)

    # def add_internal_crossover(self, locationInA, B, locationInB):
    #     j = Crossover( [self, B], [locationInA, locationInB] )
    #     self._join(B,j)


    # def stack_end(self, myEnd):
    #     ## Perhaps this should not really be possible; these ends should be part of same helix
    #     ...

    # def connect_strand(self, other):
    #     ...
        
    # def break_apart(self):
    #     """Break into smaller pieces so that "crossovers" are only at the ends"""
    #     ...

class SingleStrandedSegment(Segment):

    """ Class that describes a segment of ssDNA. When built from
    cadnano models, should not span helices """

    def __init__(self, name, num_nts, start_position = np.array((0,0,0)),
                 end_position = None, 
                 segment_model = None):

        self.distance_per_nt = 5
        Segment.__init__(self, name, num_nts, 
                         start_position,
                         end_position, 
                         segment_model)

        self.start = self.end5 = Location( self, address=0, type_= "end5" )
493
        self.end = self.end3 = Location( self, address=1, type_ = "end3" )
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511

    def connect_3end(self, end5, force_connection=False):
        self._connect_end( end5,  _5_to_3 = False, force_connection = force_connection )

    def connect_5end(self, end3, force_connection=False):
        self._connect_end( end3,  _5_to_3 = True, force_connection = force_connection )

    def _connect_end(self, other, _5_to_3, force_connection):
        assert( isinstance(other, Location) )
        if _5_to_3 == True:
            my_end = self.end5
            assert( other.type_ == "end3" )
        else:
            my_end = self.end3
            assert( other.type_ == "end5" )

        self._connect( other.container, Connection( my_end, other, type_="intrahelical" ) )

512
513
    def _get_num_beads(self, contour, max_basepairs_per_bead, max_nucleotides_per_bead):
        return int(contour*self.num_nts // max_nucleotides_per_bead)
cmaffeo2's avatar
cmaffeo2 committed
514

515
516
    def _generate_one_bead(self, contour_position, nts):
        pos = self.contour_to_position(contour_position)
517
518
519
520
521
        b = SegmentParticle( Segment.ssDNA_particle, pos, nts,
                             num_nts=nts, parent=self,
                             contour_position=contour_position )
        self._add_bead(b)
        return b
522
523

    def _assign_particles_to_locations(self):
524
525
526
527
528
529
        if self.start.particle is None:
            assert(self.beads[0].parent is not None)
            self.start.particle = self.beads[0]
        if self.end.particle is None:
            assert(self.beads[-1].parent is not None)
            self.end.particle = self.beads[-1]
530
531
532
533
534
535

    def _generate_atomic(self, atomic_model):
        ...
    

class SegmentModel(ArbdModel):
cmaffeo2's avatar
cmaffeo2 committed
536
537
538
    def __init__(self, segments=[], local_twist=True,
                 max_basepairs_per_bead=7,
                 max_nucleotides_per_bead=4,
539
540
541
                 dimensions=(1000,1000,1000), temperature=291,
                 timestep=50e-6, cutoff=50, 
                 decompPeriod=10000, pairlistDistance=None, 
542
543
544
                 nonbondedResolution=0,DEBUG=0):
        self.DEBUG = DEBUG
        if DEBUG > 0: print("Building ARBD Model")
545
546
547
548
549
        ArbdModel.__init__(self,segments,
                           dimensions, temperature, timestep, cutoff, 
                           decompPeriod, pairlistDistance=None,
                           nonbondedResolution=0)

cmaffeo2's avatar
cmaffeo2 committed
550
551
        # self.max_basepairs_per_bead = max_basepairs_per_bead     # dsDNA
        # self.max_nucleotides_per_bead = max_nucleotides_per_bead # ssDNA
552
553
554
555
        self.children = self.segments = segments

        self._bonded_potential = dict() # cache bonded potentials

556
        self._generate_bead_model( max_basepairs_per_bead, max_nucleotides_per_bead, local_twist)
557
558
559

        self.useNonbondedScheme( nbDnaScheme )

560

cmaffeo2's avatar
cmaffeo2 committed
561
    def get_connections(self,type_=None,exclude=[]):
562
563
564
565
        """ Find all connections in model, without double-counting """
        added=set()
        ret=[]
        for s in self.segments:
cmaffeo2's avatar
cmaffeo2 committed
566
            items = [e for e in s.get_connections_and_locations(type_,exclude=exclude) if e[0] not in added]
567
568
569
            added.update([e[0] for e in items])
            ret.extend( items )
        return ret
570
    
571
    def _recursively_get_beads_within_bonds(self,b1,bonds,done=[]):
572
        ret = []
573
574
575
576
577
578
579
580
581
        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 )
582
583
        return ret

584
585
586
587
588
    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)

589
590
        ret = []
        for s in self.segments:
591
592
593
594
595
            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)
596
597
        return ret

598

599
600
    def _get_intrahelical_angle_beads(self):
        return self._get_intrahelical_beads(num=3)
601

cmaffeo2's avatar
cmaffeo2 committed
602
    def _get_potential(self, type_, kSpring, d, max_potential = None):
603
604
605
        key = (type_,kSpring,d)
        if key not in self._bonded_potential:
            if type_ == "bond":
606
                self._bonded_potential[key] = HarmonicBond(kSpring,d, rRange=(0,500), max_potential=max_potential)
607
            elif type_ == "angle":
cmaffeo2's avatar
cmaffeo2 committed
608
609
                self._bonded_potential[key] = HarmonicAngle(kSpring,d, max_potential=max_potential)
                # , resolution = 1, maxForce=0.1)
610
            elif type_ == "dihedral":
cmaffeo2's avatar
cmaffeo2 committed
611
                self._bonded_potential[key] = HarmonicDihedral(kSpring,d, max_potential=max_potential)
612
613
614
615
616
617
618
            else:
                raise Exception("Unhandled potential type '%s'" % type_)
        return self._bonded_potential[key]
    def get_bond_potential(self, kSpring, d):
        return self._get_potential("bond", kSpring, d)
    def get_angle_potential(self, kSpring, d):
        return self._get_potential("angle", kSpring, d)
cmaffeo2's avatar
cmaffeo2 committed
619
620
621
622
    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)
623
624


cmaffeo2's avatar
cmaffeo2 committed
625
626
627
    def _getParent(self, *beads ):
        ## TODO: test
        if np.all( [b1.parent == b2.parent 
628
                    for b1,b2 in zip(beads[:-1],beads[1:])] ):
cmaffeo2's avatar
cmaffeo2 committed
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
            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
650
651
652
653
654
655
656
657
658

    # def _update_segment_positions(self, bead_coordinates):
    #     """ Set new function for each segments functions
    #     contour_to_position and contour_to_orientation """
        
    #     dsDnaHelixNeighborDist=50
    #     dsDnaAllNeighborDist=30
    #     ssDnaHelixNeighborDist=25
    #     ssDnaAllNeighborDist=25
cmaffeo2's avatar
cmaffeo2 committed
659
        
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
    #     beads = [b in s.beads for s in self.segments]
    #     positions = np.array([b.position for b in beads])
    #     neighborhood = dict()

    #     ## Assign neighborhood to each bead
    #     for b in beads:
    #         dists = b.position[np.newaxis,:] - positions
    #         dists = np.linalg.norm(dists, axis=-1)
    #         neighborhood[b] = np.where( dists < 50 )

    """ Mapping between different resolution models """
    def _clear_beads(self):
        for s in self.segments:
            s.clear_all()
        self.clear_all(keep_children=True)
675
676
677
678
679
680
681
682
683
684
        assert( len([b for b in self]) == 0 )
        locParticles = []
        # for c,A,B in self.get_connections():
        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(A.particle)
        assert( len(locParticles) == 0 )
        assert( len([b for s in self.segments for b in s.beads]) == 0 )
685
686
687
688

    def _update_segment_positions(self, bead_coordinates):
        """ Set new function for each segments functions
        contour_to_position and contour_to_orientation """
cmaffeo2's avatar
cmaffeo2 committed
689

690
        for s in self.segments:
691
692
693
694
695
696
697
698
699
            ## TODO: may need to make spline on helices continuously differentiable
            # beads = s.beads # [b for b in s.beads]
            beads = list(set(s.beads + [A.particle for c,A,B in s.get_connections_and_locations("intrahelical")]))
            contours = [b.get_contour_position(s) for b in beads]

            cb = sorted( zip(contours,beads), key=lambda a:a[0] )
            beads = [b for c,b in cb] 
            contours = [c for c,b in cb] 

700
701
702
703
            ids = [b.idx for b in beads]
            
            """ Get positions """
            positions = bead_coordinates[ids,:].T
704
705
706
707
708
709
710

            ## TODO: determine whether having beads is an issue 
            try:
                tck, u = interpolate.splprep( positions, u=contours, s=0, k=3 )
            except:
                tck, u = interpolate.splprep( positions, u=contours, s=0, k=1 )

711
712
713
            s.position_spline_params = tck

            """ Get twist """
714
715
716
717
718
719
            cb = [e for e in cb if 'orientation_bead' in e[1].__dict__]
            beads = [b for c,b in cb] 
            contours = [c for c,b in cb] 
            ids = [b.idx for b in beads]
            # if 'orientation_bead' in beads[0].__dict__:
            if len(beads) > 3:
720
721
722
723
724
725
726
727
728
729
                tangents = s.contour_to_tangent(contours)
                quats = []
                for b,t in zip(beads,tangents):
                    o = b.orientation_bead
                    angleVec = o.position - b.position
                    angleVec = angleVec - angleVec.dot(t)*t
                    angleVec = angleVec/np.linalg.norm(angleVec)
                    y = np.cross(t,angleVec)
                    quats.append( quaternion_from_matrix( np.array([t,y,angleVec])) )
                quats = np.array(quats)
730
731
732
733
                try:
                    tck, u = interpolate.splprep( quats.T, u=contours, s=0, k=3 )
                except:
                    tck, u = interpolate.splprep( quats.T, u=contours, s=0, k=1 )
734
735
736
737
738
739
                s.quaternion_spline_params = tck


            ## TODO: set twist

    def _generate_bead_model(self,
740
                             max_basepairs_per_bead = 7,
cmaffeo2's avatar
cmaffeo2 committed
741
                             max_nucleotides_per_bead = 4,
742
                             local_twist=False):
743

744
        segments = self.segments
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
        for s in segments:
            s.local_twist = local_twist
            
        """ Generate beads at junctions """
        if self.DEBUG: print( "Adding intrahelical beads at junctions" )
        ## Loop through all connections, generate beads at appropriate locations
        for c,A,B in self.get_connections("intrahelical"):
            s1,s2 = [l.container for l in (A,B)]
            if isinstance(s1,DoubleStrandedSegment) and isinstance(s2,DoubleStrandedSegment):
                assert( A.particle is None )
                assert( B.particle is None )

                ## TODO: offload the work here to s1
                a1,a2 = [l.address   for l in (A,B)]
                a1,a2 = [a - (0.5/s.num_nts) if a == 0 else a + (0.5/s.num_nts) for a,s in zip((a1,a2),(s1,s2))]

                b = s1._generate_one_bead(a1,0)
                A.particle = B.particle = b
763

764
765
766
767
768
769
770
771
772
            else:
                ## TODO fix this for ssDNA vs dsDNA
                a1,a2 = [l.address   for l in (A,B)]
                a1,a2 = [a - (0.5/s.num_nts) if a == 0 else a + (0.5/s.num_nts) for a,s in zip((a1,a2),(s1,s2))]

                b = s1._generate_one_bead(a1,0)
                A.particle = B.particle = b
                ...

cmaffeo2's avatar
cmaffeo2 committed
773
774
775
776
777
778
779
780
781
782
783
784
785
        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
            a1,a2 = [l.address   for l in (A,B)]
            ## TODO: if existing particle of same type is very nearby, use that instead
            A.particle = s1._generate_one_bead(a1,0)
            B.particle = s2._generate_one_bead(a2,0)

786
787
788
789
790
791
792
        """ 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 """
793
        if self.DEBUG: print("Generating beads")
794
        for s in segments:
cmaffeo2's avatar
cmaffeo2 committed
795
            s._generate_beads( self, max_basepairs_per_bead, max_nucleotides_per_bead )
796

797
798
799
800
801
802
803
804
805
806
807
808
809
810
        # """ Combine beads at junctions as needed """
        # for c,A,B in self.get_connections():
        #    ...

        """ 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
                continue
            else:
                for b in (b1,b2): assert( b is not None )
                b1.intrahelical_neighbors.append(b2)
                b2.intrahelical_neighbors.append(b1)
811
812

        """ Reassign bead types """
813
        if self.DEBUG: print("Assigning bead types")
814
815
816
        beadtype_s = dict()
        for segment in segments:
            for b in segment:
817
                b.num_nts = np.around( b.num_nts, decimals=1 )
818
819
820
821
822
823
824
825
826
                key = (b.type_.name[0].upper(), b.num_nts)
                if key in beadtype_s:
                    b.type_ = beadtype_s[key]
                else:
                    t = deepcopy(b.type_)
                    if key[0] == "D":
                        t.__dict__["nts"] = b.num_nts*2
                    elif key[0] == "S":
                        t.__dict__["nts"] = b.num_nts
cmaffeo2's avatar
cmaffeo2 committed
827
828
                    elif key[0] == "O":
                        t.__dict__["nts"] = b.num_nts
829
830
                    else:
                        raise Exception("TODO")
cmaffeo2's avatar
cmaffeo2 committed
831
                    # print(t.nts)
832
                    t.name = t.name + "%03d" % (10*t.nts)
833
834
                    beadtype_s[key] = b.type_ = t

835
836
837
        """ Update bead indices """
        self._countParticleTypes() # probably not needed here
        self._updateParticleOrder()
838

839
        """ Add intrahelical bond potentials """
840
        if self.DEBUG: print("Adding intrahelical bond potentials")
cmaffeo2's avatar
cmaffeo2 committed
841
        dists = dict()          # intrahelical distances built for later use
842
843
844
        intra_beads = self._get_intrahelical_beads() 
        if self.DEBUG: print("  Adding %d bonds" % len(intra_beads))
        for b1,b2 in intra_beads:
cmaffeo2's avatar
cmaffeo2 committed
845
            parent = self._getParent(b1,b2)
846
847
848

            ## TODO: could be sligtly smarter about sep
            sep = 0.5*(b1.num_nts+b2.num_nts)
cmaffeo2's avatar
cmaffeo2 committed
849

850
            conversion = 0.014393265 # units "pN/AA" kcal_mol/AA^2
851
            if b1.type_.name[0] == "D" and b2.type_.name[0] == "D":
852
                elastic_modulus = 1000 # pN http://markolab.bmbcb.northwestern.edu/marko/Cocco.CRP.02.pdf
853
                d = 3.4*sep
854
                k = conversion*elastic_modulus/d
855
            else:
856
857
                ## TODO: get better numbers our ssDNA model
                elastic_modulus = 800 # pN http://markolab.bmbcb.northwestern.edu/marko/Cocco.CRP.02.pdf
858
                d = 5*sep
859
                k = conversion*elastic_modulus/d
860
                # print(sep,d,k)
861
862
863
864
865
866
867
868
869
              
            if b1 not in dists:
                dists[b1] = []
            if b2 not in dists:
                dists[b2] = []
            dists[b1].append([b2,sep])
            dists[b2].append([b1,sep])

            # dists[[b1,b2]] = dists[[b2,b1]] = sep
870
871
            bond = self.get_bond_potential(k,d)
            parent.add_bond( b1, b2, bond, exclude=True )
872
873

        """ Add intrahelical angle potentials """
874
        if self.DEBUG: print("Adding intrahelical angle potentials")
875
        for b1,b2,b3 in self._get_intrahelical_angle_beads():
876
877
            ## TODO: could be slightly smarter about sep
            sep = 0.5*b1.num_nts+b2.num_nts+0.5*b3.num_nts
cmaffeo2's avatar
cmaffeo2 committed
878
            parent = self._getParent(b1,b2,b3)
879

880
881
882
883
884
885
            kT = 0.58622522         # kcal/mol
            if b1.type_.name[0] == "D" and b2.type_.name[0] == "D" and b3.type_.name[0] == "D":
                ## <cos(q)> = exp(-s/Lp) = integrate( x^4 exp(-A x^2) / 2, {x, 0, pi} ) / integrate( x^2 exp(-A x^2), {x, 0, pi} )
                ## <cos(q)> ~ 1 - 3/4A                                                                                            
                ## where A = k_spring / (2 kT)                                                                                    
                k = 1.5 * kT * (1.0 / (1-np.exp(-float(sep)/147))) * 0.00030461742; # kcal_mol/degree^2
cmaffeo2's avatar
cmaffeo2 committed
886
887
                if local_twist:
                    k *= 0.5    # halve because orientation beads have similar springs
888
889
            else:
                ## TODO: get correct number from ssDNA model
cmaffeo2's avatar
cmaffeo2 committed
890
                k = 1.5 * kT * (1.0 / (1-np.exp(-float(sep)/3))) * 0.00030461742; # kcal_mol/degree^2
891

892
893
894
895
            angle = self.get_angle_potential(k,180)
            parent.add_angle( b1, b2, b3, angle )

        """ Add intrahelical exclusions """
896
        if self.DEBUG: print("Adding intrahelical exclusions")
897
898
899
900
901
902
903
904
905
906
907
        beads = dists.keys()
        def _recursively_get_beads_within(b1,d,done=[]):
            ret = []
            for b2,sep in dists[b1]:
                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
908

909
910
911
        exclusions = set()
        for b1 in beads:
            exclusions.update( [(b1,b) for b in _recursively_get_beads_within(b1, 20, done=[b1])] )
912
913

        if self.DEBUG: print("Adding %d exclusions" % len(exclusions))
914
        for b1,b2 in exclusions:
cmaffeo2's avatar
cmaffeo2 committed
915
            parent = self._getParent(b1,b2)
916
            parent.add_exclusion( b1, b2 )
cmaffeo2's avatar
cmaffeo2 committed
917
918
919

        """ Twist potentials """
        if local_twist:
920
            if self.DEBUG: print("Adding twist potentials")
cmaffeo2's avatar
cmaffeo2 committed
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954
955

            ## TODO: decide whether to add bond here
            # """Add bonds between orientation bead and parent"""
            # for s in self.segments:
            #     for b,o in zip(s.children[::2],s.children[1::2]):
            #         s.add_bond(
                    

            for b1 in beads:
                if "orientation_bead" not in b1.__dict__: continue
                for b2,sep in dists[b1]:
                    if "orientation_bead" not in b2.__dict__: continue

                    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 """
                    k = (1.0/2) * 1.5 * kT * (1.0 / (1-np.exp(-float(sep)/147))) * 0.00030461742; # kcal_mol/degree^2
                    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:
                        raise Exception("The twist between beads is too large")
                        
                    k = self._get_twist_spring_constant(sep)
                    pot = self.get_dihedral_potential(k,angle,max_potential=1)
                    parent.add_dihedral(o1,b1,b2,o2, pot)

956
        """ Add connection potentials """
957
958
959
960
        for c,A,B in self.get_connections("terminal_crossover"):
            b1,b2 = [loc.particle for loc in (c.A,c.B)]
            pot = self.get_bond_potential(4,18.5)
            self.add_bond(b1,b2, pot)
961

cmaffeo2's avatar
cmaffeo2 committed
962
963
964
965
966
967
968
969
970
971
972
973
974
975
976
977
978
979
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
1000
        for c,A,B in self.get_connections("crossover"):
            b1,b2 = [loc.particle for loc in (c.A,c.B)]
            pot = self.get_bond_potential(4,18.5)
            self.add_bond(b1,b2, pot)

            if not local_twist:
                ## TODO
                ...
            else:
                ## TODO: fwd/rev
                k = (1.0/2) * 1.5 * kT * (1.0 / (1-np.exp(-float(1)/147))) * 0.00030461742; # kcal_mol/degree^2
                if 'orientation_bead' in b1.__dict__:
                    t0 = 90 + 60
                    # if f1: t0 -= 120
                    o = b1.orientation_bead
                    pot = self.get_angle_potential(k,t0)
                    self.add_angle( o,b1,b2, pot )
                else:
                    t0 = 90 + 60
                    # if f2: t0 -= 120
                    o = b2.orientation_bead
                    pot = self.get_angle_potential(k,t0)
                    self.add_angle( b1,b2,o, pot )


                u1,u2 = [b.intrahelical_neighbors[-1] for b in (b1,b2)] # TODO: fix this
                d1,d2 = [b.intrahelical_neighbors[0] for b in (b1,b2)] # TODO: fix this

                ## TODO make k depend on sep
                k = (1.0/2) * 1.5 * kT * (1.0 / (1-np.exp(-float(1)/147))) * 0.00030461742; # kcal_mol/degree^2
                t0 = 90
                pot = self.get_dihedral_potential(k,t0)
                if 'orientation_bead' in b1.__dict__:
                    o1 = b1.orientation_bead
                    if u2 is not None:
                        self.add_dihedral( o1,b1,b2,u2, pot )
                    elif d2 is not None:
                        self.add_dihedral( o2,b2,b1,d2, pot )
                if 'orientation_bead' in b2.__dict__:
For faster browsing, not all history is shown. View entire blame