segmentmodel.py 105 KB
Newer Older
cmaffeo2's avatar
cmaffeo2 committed
1
import pdb
2
import numpy as np
3
import random
4
5
6
from .model.arbdmodel import PointParticle, ParticleType, Group, ArbdModel
from .coords import rotationAboutAxis, quaternion_from_matrix, quaternion_to_matrix
from .model.nonbonded import *
7
from copy import copy, deepcopy
8
from .model.nbPot import nbDnaScheme
9

cmaffeo2's avatar
cmaffeo2 committed
10
11
from scipy.special import erf
import scipy.optimize as opt
12
from scipy import interpolate
cmaffeo2's avatar
cmaffeo2 committed
13

14
15
from .model.CanonicalNucleotideAtoms import canonicalNtFwd, canonicalNtRev, seqComplement
from .model.CanonicalNucleotideAtoms import enmTemplateHC, enmTemplateSQ, enmCorrectionsHC
cmaffeo2's avatar
cmaffeo2 committed
16

17
# import pdb
18
"""
cmaffeo2's avatar
cmaffeo2 committed
19
TODO:
cmaffeo2's avatar
cmaffeo2 committed
20
 + fix handling of crossovers for atomic representation
cmaffeo2's avatar
cmaffeo2 committed
21
 + map to atomic representation
22
    + add nicks
cmaffeo2's avatar
cmaffeo2 committed
23
    + transform ssDNA nucleotides 
cmaffeo2's avatar
cmaffeo2 committed
24
    - shrink ssDNA
cmaffeo2's avatar
cmaffeo2 committed
25
    + shrink dsDNA backbone
26
    + make orientation continuous
cmaffeo2's avatar
cmaffeo2 committed
27
    + sequence
28
    - handle circular dna
29
 + ensure crossover bead potentials aren't applied twice 
30
 + remove performance bottlenecks
31
 - test for large systems
cmaffeo2's avatar
cmaffeo2 committed
32
 + assign sequence
33
 + ENM
34
35
 - rework Location class 
 - remove recursive calls
36
 - document
37
 - add unit test of helices connected to themselves
38
"""
cmaffeo2's avatar
cmaffeo2 committed
39
40
class CircularDnaError(Exception):
    pass
41

cmaffeo2's avatar
cmaffeo2 committed
42
43
44
class ParticleNotConnectedError(Exception):
    pass

45
46
class Location():
    """ Site for connection within an object """
47
    def __init__(self, container, address, type_, on_fwd_strand = True):
48
        ## TODO: remove cyclic references(?)
49
        self.container = container
cmaffeo2's avatar
cmaffeo2 committed
50
        self.address = address  # represents position along contour length in segment
cmaffeo2's avatar
cmaffeo2 committed
51
        # assert( type_ in ("end3","end5") ) # TODO remove or make conditional
52
        self.on_fwd_strand = on_fwd_strand
53
54
        self.type_ = type_
        self.particle = None
55
        self.connection = None
56
        self.is_3prime_side_of_connection = None
57

58
59
        self.prev_in_strand = None
        self.next_in_strand = None
60
61
        
        self.combine = None     # some locations might be combined in bead model 
62
63
64
65
66
67
68

    def get_connected_location(self):
        if self.connection is None:
            return None
        else:
            return self.connection.other(self)

69
    def set_connection(self, connection, is_3prime_side_of_connection):
70
        self.connection = connection # TODO weakref? 
71
        self.is_3prime_side_of_connection = is_3prime_side_of_connection
72

73
74
75
76
77
78
79
    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:
80
                pos = self.container.num_nt-1
81
82
83
84
            else:
                raise
        return pos

85
86
87
88
89
90
91
    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)
        
92
93
94
95
96
97
98
99
100
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_
        
101
102
103
104
105
106
107
    def other(self, location):
        if location is self.A:
            return self.B
        elif location is self.B:
            return self.A
        else:
            raise Exception("OutOfBoundsError")
cmaffeo2's avatar
cmaffeo2 committed
108

109
110
111
112
113
114
    def delete(self):
        self.A.container.connections.remove(self)
        self.B.container.connections.remove(self)
        self.A.connection = None
        self.B.connection = None

cmaffeo2's avatar
cmaffeo2 committed
115
116
117
118
    def __repr__(self):
        return "<Connection {}--{}--{}]>".format( self.A, self.type_, self.B )
        

119
        
120
121
122
# class ConnectableElement(Transformable):
class ConnectableElement():
    """ Abstract base class """
cmaffeo2's avatar
cmaffeo2 committed
123
124
125
126
    def __init__(self, connection_locations=None, connections=None):
        if connection_locations is None: connection_locations = []
        if connections is None: connections = []

127
128
        ## TODO decide on names
        self.locations = self.connection_locations = connection_locations
129
130
        self.connections = connections

cmaffeo2's avatar
cmaffeo2 committed
131
    def get_locations(self, type_=None, exclude=()):
132
133
134
135
136
137
138
139
        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] ) )
140
141
142
143
        return locs

    def get_location_at(self, address, on_fwd_strand=True, new_type="crossover"):
        loc = None
144
        if (self.num_nt == 1):
145
146
147
148
149
150
151
            # 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
cmaffeo2's avatar
cmaffeo2 committed
152
            # assert( loc is not None )
153
154
155
156
157
158
159
160
        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
161

cmaffeo2's avatar
cmaffeo2 committed
162
    def get_connections_and_locations(self, connection_type=None, exclude=()):
163
164
        """ Returns a list with each entry of the form:
            connection, location_in_self, location_in_other """
165
        type_ = connection_type
166
167
        ret = []
        for c in self.connections:
168
            if (type_ is None or c.type_ == type_) and c.type_ not in exclude:
169
                if   c.A.container is self:
170
                    ret.append( [c, c.A, c.B] )
171
                elif c.B.container is self:
172
173
                    ret.append( [c, c.B, c.A] )
                else:
174
175
                    import pdb
                    pdb.set_trace()
176
177
178
                    raise Exception("Object contains connection that fails to refer to object")
        return ret

179
    def _connect(self, other, connection, in_3prime_direction=None):
180
181
        ## TODO fix circular references        
        A,B = [connection.A, connection.B]
182
183
184
185
        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
            
186
        A.connection = B.connection = connection
187
188
        self.connections.append(connection)
        other.connections.append(connection)
189
190
191
192
193
194
        l = A.container.locations
        if A not in l: l.append(A)
        l = B.container.locations
        if B not in l: l.append(B)
        

195
196
    # def _find_connections(self, loc):
    #     return [c for c in self.connections if c.A == loc or c.B == loc]
197
198
199

class SegmentParticle(PointParticle):
    def __init__(self, type_, position, name="A", segname="A", **kwargs):
200
        self.name = name
201
202
203
204
        self.contour_position = None
        PointParticle.__init__(self, type_, position, name=name, segname=segname, **kwargs)
        self.intrahelical_neighbors = []
        self.other_neighbors = []
cmaffeo2's avatar
cmaffeo2 committed
205
        self.locations = []
206
207
208

    def get_intrahelical_above(self):
        """ Returns bead directly above self """
209
        # assert( len(self.intrahelical_neighbors) <= 2 )
210
211
212
213
214
215
        for b in self.intrahelical_neighbors:
            if b.get_contour_position(self.parent) > self.contour_position:
                return b

    def get_intrahelical_below(self):
        """ Returns bead directly below self """
216
        # assert( len(self.intrahelical_neighbors) <= 2 )
217
218
219
220
        for b in self.intrahelical_neighbors:
            if b.get_contour_position(self.parent) < self.contour_position:
                return b

cmaffeo2's avatar
cmaffeo2 committed
221
    def _neighbor_should_be_added(self,b):
222
223
224
        if type(self.parent) != type(b.parent):
            return True

cmaffeo2's avatar
cmaffeo2 committed
225
226
227
228
        c1 = self.contour_position
        c2 = b.get_contour_position(self.parent)
        if c2 < c1:
            b0 = self.get_intrahelical_below()
229
        else:
cmaffeo2's avatar
cmaffeo2 committed
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
            b0 = self.get_intrahelical_above()

        if b0 is not None:            
            c0 = b0.get_contour_position(self.parent)
            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:
247
248
            # assert(len(b.intrahelical_neighbors) <= 1)
            # assert(len(self.intrahelical_neighbors) <= 1)
cmaffeo2's avatar
cmaffeo2 committed
249
250
            self.intrahelical_neighbors.append(b)
            b.intrahelical_neighbors.append(self)
251

cmaffeo2's avatar
cmaffeo2 committed
252
253
254
255
256
257
258
259
260
261
    def get_nt_position(self, seg):
        """ Returns the "address" of the nucleotide relative to seg in
        nucleotides, taking the shortest (intrahelical) contour length route to seg
        """
        if seg == self.parent:
            return seg.contour_to_nt_pos(self.contour_position)
        else:
            pos = self.get_contour_position(seg)
            return seg.contour_to_nt_pos(pos)

262
263
264
265
    def get_contour_position(self,seg):
        if seg == self.parent:
            return self.contour_position
        else:
cmaffeo2's avatar
cmaffeo2 committed
266
267
268
269
270
            cutoff = 30*3
            target_seg = seg

            ## depth-first search
            ## TODO cache distances to nearby locations?
cmaffeo2's avatar
cmaffeo2 committed
271
            def descend_search_tree(seg, contour_in_seg, distance=0, visited_segs=None):
cmaffeo2's avatar
cmaffeo2 committed
272
                nonlocal cutoff
cmaffeo2's avatar
cmaffeo2 committed
273
                if visited_segs is None: visited_segs = []
cmaffeo2's avatar
cmaffeo2 committed
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317

                if seg == target_seg:
                    # pdb.set_trace()
                    ## Found a segment in our target
                    sign = (contour_in_seg == 1) - (contour_in_seg == 0)
                    assert( sign in (1,-1) )
                    if distance < cutoff: # TODO: check if this does anything
                        cutoff = distance
                    return [[distance, contour_in_seg+sign*seg.nt_pos_to_contour(distance)]]
                if distance > cutoff:
                    return None
                    
                ret_list = []
                ## Find intrahelical locations in seg that we might pass through
                for c,A,B in seg.get_connections_and_locations("intrahelical"):
                    if B.container in visited_segs: continue
                    dx = seg.contour_to_nt_pos( np.abs(A.address-contour_in_seg),
                                                round_nt=False) 
                    results = descend_search_tree( B.container, B.address,
                                                   distance+dx, visited_segs + [seg] )
                    if results is not None:
                        ret_list.extend( results )
                return ret_list

            results = 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
            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)) )
            
318
319

## TODO break this class into smaller, better encapsulated pieces
320
321
322
323
324
325
326
327
328
329
330
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
331
332
333
334
335
    orientation_particle = ParticleType("O",
                                        diffusivity = 100,
                                        mass = 300,
                                        radius = 1,
                                    )
336

cmaffeo2's avatar
cmaffeo2 committed
337
    # orientation_bond = HarmonicBond(10,2)
338
    orientation_bond = HarmonicBond(30,1.5, rRange = (0,500) )
339
340
341
342
343
344
345

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

346
    def __init__(self, name, num_nt, 
cmaffeo2's avatar
cmaffeo2 committed
347
                 start_position = None,
348
349
350
                 end_position = None, 
                 segment_model = None):

cmaffeo2's avatar
cmaffeo2 committed
351
352
        if start_position is None: start_position = np.array((0,0,0))

353
        Group.__init__(self, name, children=[])
354
        ConnectableElement.__init__(self, connection_locations=[], connections=[])
355

356
        self.resname = name
cmaffeo2's avatar
cmaffeo2 committed
357
358
359
360
361
        self.start_orientation = None
        self.twist_per_nt = 0

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

362
363
364
        self._bead_model_generation = 0    # TODO: remove?
        self.segment_model = segment_model # TODO: remove?

365
366
367
368
        self.strand_pieces = dict()
        for d in ('fwd','rev'):
            self.strand_pieces[d] = []

369
        self.num_nt = int(num_nt)
370
        if end_position is None:
371
            end_position = np.array((0,0,self.distance_per_nt*num_nt)) + start_position
372
373
374
        self.start_position = start_position
        self.end_position = end_position

375
        ## Set up interpolation for positions
376
377
378
379
        self._set_splines_from_ends()

        self.sequence = None

380
381
382
    def __repr__(self):
        return "<{} {}[{:d}]>".format( type(self), self.name, self.num_nt )

383
384

    def _set_splines_from_ends(self):
385
386
387
        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
388
        self.quaternion_spline_params = None
389

390

391
392
393
394
395
    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
396

397
    def contour_to_nt_pos(self, contour_pos, round_nt=False):
398
        nt = contour_pos*(self.num_nt) - 0.5
399
        if round_nt:
cmaffeo2's avatar
cmaffeo2 committed
400
            assert( np.isclose(np.around(nt),nt) )
401
402
403
            nt = np.around(nt)
        return nt

404
    def nt_pos_to_contour(self,nt_pos):
405
        return (nt_pos+0.5)/(self.num_nt)
406

407
408
409
410
411
412
413
    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 )
414
415
        t = (t / np.linalg.norm(t,axis=0))
        return t.T
416
417
418
        

    def contour_to_orientation(self,s):
419
        assert( isinstance(s,float) or isinstance(s,int) or len(s) == 1 )   # TODO make vectorized version
420

421
422
423
424
425
        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)
426
            zAxis = np.array((0,0,1))
427
428

            if rotAxisL > 0.001:
429
430
431
                theta = np.arcsin(rotAxisL) * 180/np.pi
                if axis.dot(zAxis) < 0: theta = 180-theta
                orientation0 = rotationAboutAxis( rotAxis/rotAxisL, theta, normalizeAxis=False ).T
432
            else:
433
434
                orientation0 = np.eye(3) if axis.dot(zAxis) > 0 else \
                               rotationAboutAxis( np.array((1,0,0)), 180, normalizeAxis=False )
435
436
437
438
439
440
            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 )
            if len(q) > 1: q = np.array(q).T # TODO: is this needed?
            orientation = quaternion_to_matrix(q)
441

442
        return orientation
443

cmaffeo2's avatar
cmaffeo2 committed
444
    def get_contour_sorted_connections_and_locations(self,type_):
cmaffeo2's avatar
cmaffeo2 committed
445
        sort_fn = lambda c: c[1].address
cmaffeo2's avatar
cmaffeo2 committed
446
        cl = self.get_connections_and_locations(type_)
cmaffeo2's avatar
cmaffeo2 committed
447
        return sorted(cl, key=sort_fn)
448
449
450
    
    def randomize_unset_sequence(self):
        bases = list(seqComplement.keys())
451
        # bases = ['T']        ## FOR DEBUG
452
        if self.sequence is None:
453
            self.sequence = [random.choice(bases) for i in range(self.num_nt)]
454
        else:
455
            assert(len(self.sequence) == self.num_nt) # TODO move
456
457
458
            for i in range(len(self.sequence)):
                if self.sequence[i] is None:
                    self.sequence[i] = random.choice(bases)
459

cmaffeo2's avatar
cmaffeo2 committed
460
461
462
    def _get_num_beads(self, max_basepairs_per_bead, max_nucleotides_per_bead ):
        raise NotImplementedError

463
    def _generate_one_bead(self, contour_position, nts):
464
465
        raise NotImplementedError

466
    def _generate_atomic_nucleotide(self, contour_position, is_fwd, seq, scale):
cmaffeo2's avatar
cmaffeo2 committed
467
468
469
470
471
        """ 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)
472
        orientation = self.contour_to_orientation(contour_position)
cmaffeo2's avatar
cmaffeo2 committed
473

474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
        """ 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                            
        """
cmaffeo2's avatar
cmaffeo2 committed
492
        key = seq
493
494
        nt_dict = canonicalNtFwd if is_fwd else canonicalNtRev

495
        atoms = nt_dict[ key ].generate() # TODO: clone?
cmaffeo2's avatar
cmaffeo2 committed
496
                        
cmaffeo2's avatar
cmaffeo2 committed
497
        atoms.orientation = orientation.dot(atoms.orientation)
498
499
500
501
502
        if isinstance(self, SingleStrandedSegment):
            if scale is not None and scale != 1:
                for a in atoms:
                    a.position = scale*a.position
                    a.beta = 0
503
            atoms.position = pos - atoms.atoms_by_name["C1'"].collapsedPosition()
504
505
506
507
508
509
510
511
512
513
514
        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
                        a.beta = 0
            atoms.position = pos
cmaffeo2's avatar
cmaffeo2 committed
515
516

        return atoms
517

518
519
    def add_location(self, nt, type_, on_fwd_strand=True):
        ## Create location if needed, add to segment
520
        c = self.nt_pos_to_contour(nt)
521
522
523
524
525
526
527
        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_5prime(self, nt, on_fwd_strand=True):
528
529
        if isinstance(self,SingleStrandedSegment):
            on_fwd_strand = True
530
        self.add_location(nt,"5prime",on_fwd_strand)
531
532

    def add_3prime(self, nt, on_fwd_strand=True):
533
534
        if isinstance(self,SingleStrandedSegment):
            on_fwd_strand = True
535
        self.add_location(nt,"3prime",on_fwd_strand)
536

537
    def get_3prime_locations(self):
cmaffeo2's avatar
cmaffeo2 committed
538
        return sorted(self.get_locations("3prime"),key=lambda x: x.address)
539
    
cmaffeo2's avatar
cmaffeo2 committed
540
    def get_5prime_locations(self):
541
        ## TODO? ensure that data is consistent before _build_model calls
cmaffeo2's avatar
cmaffeo2 committed
542
        return sorted(self.get_locations("5prime"),key=lambda x: x.address)
cmaffeo2's avatar
cmaffeo2 committed
543

544
    def iterate_connections_and_locations(self, reverse=False):
cmaffeo2's avatar
cmaffeo2 committed
545
546
        ## connections to other segments
        cl = self.get_contour_sorted_connections_and_locations()
547
        if reverse:
cmaffeo2's avatar
cmaffeo2 committed
548
            cl = cl[::-1]
549
550
551
            
        for c in cl:
            yield c
cmaffeo2's avatar
cmaffeo2 committed
552

553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
    ## 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)

571
    ## TODO rename
572
    def get_strand_segment(self, nt_pos, is_fwd, move_at_least=0.5):
573
        """ Walks through locations, checking for crossovers """
574
575
576
577
        # if self.name in ("6-1","1-1"):
        #     import pdb
        #     pdb.set_trace()
        move_at_least = 0
578
579

        ## Iterate through locations
cmaffeo2's avatar
cmaffeo2 committed
580
        # locations = sorted(self.locations, key=lambda l:(l.address,not l.on_fwd_strand), reverse=(not is_fwd))
581
582
583
584
585
586
        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))
587
588
        # print(locations)

589
        for l in locations:
cmaffeo2's avatar
cmaffeo2 committed
590
591
592
593
            # TODOTODO probably okay
            if l.address == 0:
                pos = 0.0
            elif l.address == 1:
594
                pos = self.num_nt-1
cmaffeo2's avatar
cmaffeo2 committed
595
596
            else:
                pos = self.contour_to_nt_pos(l.address, round_nt=True)
597
598
599

            ## DEBUG

cmaffeo2's avatar
cmaffeo2 committed
600

601
            ## Skip locations encountered before our strand
602
603
604
605
606
607
608
609
            # 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
610
611
612

            ## Stop if we found the 3prime end
            if l.on_fwd_strand == is_fwd and l.type_ == "3prime":
613
                # print("  found end at",l)
614
                return pos, None, None, None, None
615
616
617
618
619
620
621
622

            ## 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:
623
624
                # print("  passing through",l)
                # print("from {}, connection {} to {}".format(nt_pos,l,B))
625
                Bpos = B.get_nt_pos()
626
                return pos, B.container, Bpos, B.on_fwd_strand, 0.5
627
628
629
                
            ## Stop at other strand crossovers so basepairs line up
            elif c.type_ == "crossover":
630
                if nt_pos == pos: continue
631
                # print("  pausing at",l)
632
                return pos, l.container, pos+(2*is_fwd-1), is_fwd, 0
633
634
635
636
637
638

        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

639
640
641
    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
642
        # TODO: include beads in connections?
643
644
645
        i = np.argmin((cs - contour_position)**2)

        return self.beads[i]
646

647
648
649
650
651
652
653
654
655
    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 ))

656
657
    def get_all_consecutive_beads(self, number):
        assert(number >= 1)
cmaffeo2's avatar
cmaffeo2 committed
658
        ## Assume that consecutive beads in self.beads are bonded
659
        ret = []
cmaffeo2's avatar
cmaffeo2 committed
660
661
        for i in range(len(self.beads)-number+1):
            tmp = [self.beads[i+j] for j in range(0,number)]
662
            ret.append( tmp )
663
        return ret   
664

665
666
667
    def _add_bead(self,b,set_contour=False):
        if set_contour:
            b.contour_position = b.get_contour_position(self)
668
        
669
670
671
        # assert(b.parent is None)
        if b.parent is not None:
            b.parent.children.remove(b)
672
        self.add(b)
673
674
675
676
677
678
        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)
679
            self.add(o)
680
681
682
683
684
685
686
687
            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 = []
688
689

        if True:
690
691
            ## TODO: remove this if duplicates are never found 
            # print("Searching for duplicate particles...")
692
            ## Remove duplicates, preserving order
693
694
695
696
            tmp = []
            for c in new_children:
                if c not in tmp:
                    tmp.append(c)
697
                else:
698
                    print("  DUPLICATE PARTICLE FOUND!")
699
700
            new_children = tmp

701
702
703
704
705
        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)
706
707
708
709
710
            
        # 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)
711
712
        assert(len(old_children) == len(self.children))
        assert(len(old_beads) == len(self.beads))
713

714

cmaffeo2's avatar
cmaffeo2 committed
715
    def _generate_beads(self, bead_model, max_basepairs_per_bead, max_nucleotides_per_bead):
716

717
        """ Generate beads (positions, types, etc) and bonds, angles, dihedrals, exclusions """
cmaffeo2's avatar
cmaffeo2 committed
718
        ## TODO: decide whether to remove bead_model argument
719
        ##       (currently unused)
cmaffeo2's avatar
cmaffeo2 committed
720

721
        ## First find points between-which beads must be generated
722
723
724
        # 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]
cmaffeo2's avatar
cmaffeo2 committed
725
726
        # if self.name == "31-2":
            # pdb.set_trace()
727

728
729
730
731
732
        existing_beads = {l.particle for l in self.locations if l.particle is not None}
        existing_beads = sorted( list(existing_beads), key=lambda b: b.get_contour_position(self) )
        
        if len(existing_beads) != len(set(existing_beads)):
            pdb.set_trace()
733
734
735
736
        for b in existing_beads:
            assert(b.parent is not None)

        ## Add ends if they don't exist yet
737
        ## TODOTODO: test 1 nt segments?
738
        if len(existing_beads) == 0 or existing_beads[0].get_nt_position(self) >= 0.5:
cmaffeo2's avatar
cmaffeo2 committed
739
740
            # if len(existing_beads) > 0:            
            #     assert(existing_beads[0].get_nt_position(self) >= 0.5)
741
            b = self._generate_one_bead( self.nt_pos_to_contour(0), 0)
742
            existing_beads = [b] + existing_beads
cmaffeo2's avatar
cmaffeo2 committed
743

744
745
        if existing_beads[-1].get_nt_position(self)-(self.num_nt-1) < -0.5:
            b = self._generate_one_bead( self.nt_pos_to_contour(self.num_nt-1), 0)
746
747
748
749
750
            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
751
        last = None
cmaffeo2's avatar
cmaffeo2 committed
752

753
754
        for I in range(len(existing_beads)-1):
            eb1,eb2 = [existing_beads[i] for i in (I,I+1)]
755
            assert( eb1 is not eb2 )
756

cmaffeo2's avatar
cmaffeo2 committed
757
758
759
760
            # if np.isclose(eb1.position[2], eb2.position[2]):
            #     import pdb
            #     pdb.set_trace()

761
            # print(" %s working on %d to %d" % (self.name, eb1.position[2], eb2.position[2]))
762
763
            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 )
cmaffeo2's avatar
cmaffeo2 committed
764
765
766
767
768
769

            ## 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

770
            ds = e_ds / (num_beads+1)
771
772
773
            nts = ds*self.num_nt
            eb1.num_nt += 0.5*nts
            eb2.num_nt += 0.5*nts
774
775
776
777
778
779
780

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

            s0 = eb1.get_contour_position(self)
            if last is not None:
cmaffeo2's avatar
cmaffeo2 committed
781
                last.make_intrahelical_neighbor(eb1)
782
783
784
            last = eb1
            for j in range(num_beads):
                s = ds*(j+1) + s0
785
                # if self.name in ("51-2","51-3"):
cmaffeo2's avatar
cmaffeo2 committed
786
                # if self.name in ("31-2",):
787
                #     print(" adding bead at {}".format(s))
788
789
                b = self._generate_one_bead(s,nts)

cmaffeo2's avatar
cmaffeo2 committed
790
                last.make_intrahelical_neighbor(b)
791
792
793
                last = b
                tmp_children.append(b)

cmaffeo2's avatar
cmaffeo2 committed
794
        last.make_intrahelical_neighbor(eb2)
795
796
797

        if eb2.parent == self:
            tmp_children.append(eb2)
cmaffeo2's avatar
cmaffeo2 committed
798
        # if self.name in ("31-2",):
799
        #     pdb.set_trace()
800
        self._rebuild_children(tmp_children)
801
802
803
804
805
806
807
808
809
810

    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 """

811
    def __init__(self, name, num_bp, start_position = np.array((0,0,0)),
812
813
                 end_position = None, 
                 segment_model = None,
cmaffeo2's avatar
cmaffeo2 committed
814
815
                 local_twist = False,
                 num_turns = None,
cmaffeo2's avatar
cmaffeo2 committed
816
817
                 start_orientation = None,
                 twist_persistence_length = 90 ):
cmaffeo2's avatar
cmaffeo2 committed
818
819
820
        
        self.helical_rise = 10.44
        self.distance_per_nt = 3.4
821
        Segment.__init__(self, name, num_bp,
822
823
824
                         start_position,
                         end_position, 
                         segment_model)
825
        self.num_bp = self.num_nt
826

cmaffeo2's avatar
cmaffeo2 committed
827
828
        self.local_twist = local_twist
        if num_turns is None:
829
830
            num_turns = float(num_bp) / self.helical_rise
        self.twist_per_nt = float(360 * num_turns) / num_bp
cmaffeo2's avatar
cmaffeo2 committed
831
832

        if start_orientation is None:
833
            start_orientation = np.eye(3) # np.array(((1,0,0),(0,1,0),(0,0,1)))
cmaffeo2's avatar
cmaffeo2 committed
834
        self.start_orientation = start_orientation
cmaffeo2's avatar
cmaffeo2 committed
835
        self.twist_persistence_length = twist_persistence_length
cmaffeo2's avatar
cmaffeo2 committed
836

837
838
        self.nicks = []

839
        self.start = self.start5 = Location( self, address=0, type_= "end5" )
840
        self.start3 = Location( self, address=0, type_ = "end3", on_fwd_strand=False )
841

842
843
        self.end = self.end3 = Location( self, address=1, type_ = "end3" )
        self.end5 = Location( self, address=1, type_= "end5", on_fwd_strand=False )
cmaffeo2's avatar
cmaffeo2 committed
844
845
        # for l in (self.start5,self.start3,self.end3,self.end5):
        #     self.locations.append(l)
846

847
848
849
850
851
852
853
        ## 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

854
    ## Convenience methods
855
    ## TODO: add errors if unrealistic connections are made
856
    ## TODO: make connections automatically between unconnected strands
857
    def connect_start5(self, end3, type_="intrahelical", force_connection=False):
858
859
        if isinstance(end3, SingleStrandedSegment):
            end3 = end3.end3
860
861
        self._connect_ends( self.start5, end3, type_, force_connection = force_connection )
    def connect_start3(self, end5, type_="intrahelical", force_connection=False):
862
        if isinstance(end5, SingleStrandedSegment):
863
            end5 = end5.start5
864
865
        self._connect_ends( self.start3, end5, type_, force_connection = force_connection )
    def connect_end3(self, end5, type_="intrahelical", force_connection=False):
866
        if isinstance(end5, SingleStrandedSegment):
867
            end5 = end5.start5
868
869
        self._connect_ends( self.end3, end5, type_, force_connection = force_connection )
    def connect_end5(self, end3, type_="intrahelical", force_connection=False):
870
871
        if isinstance(end3, SingleStrandedSegment):
            end3 = end3.end3
872
        self._connect_ends( self.end5, end3, type_, force_connection = force_connection )
873

874
    def add_crossover(self, nt, other, other_nt, strands_fwd=(True,False), nt_on_5prime=True, type_="crossover"):
cmaffeo2's avatar
cmaffeo2 committed
875
876
877
878
        """ Add a crossover between two helices """
        ## Validate other, nt, other_nt
        ##   TODO

879
        if isinstance(other,SingleStrandedSegment):
cmaffeo2's avatar
cmaffeo2 committed
880
            other.add_crossover(other_nt, self, nt, strands_fwd[::-1], not nt_on_5prime)
881
        else:
882

883
884
885
            ## Create locations, connections and add to segments
            c = self.nt_pos_to_contour(nt)
            assert(c >= 0 and c <= 1)
886

887
888
889
            loc = self.get_location_at(c, strands_fwd[0])

            c = other.nt_pos_to_contour(other_nt)
cmaffeo2's avatar
cmaffeo2 committed
890
            # TODOTODO: may need to subtract or add a little depending on 3prime/5prime
891
892
            assert(c >= 0 and c <= 1)
            other_loc = other.get_location_at(c, strands_fwd[1])
893
            self._connect(other, Connection( loc, other_loc, type_=type_ ))
cmaffeo2's avatar
cmaffeo2 committed
894
895
896
897
898
899
            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
cmaffeo2's avatar
cmaffeo2 committed
900

901
    ## Real work
902
    def _connect_ends(self, end1, end2, type_, force_connection):
903
        ## TODO remove self?
904
905
906
907
908
        ## validate the input
        for end in (end1, end2):
            assert( isinstance(end, Location) )
            assert( end.type_ in ("end3","end5") )
        assert( end1.type_ != end2.type_ )
909
910
911
912
913
914
915
916
917

        ## 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()

918
        ## Create and add connection
cmaffeo2's avatar
cmaffeo2 committed
919
        if end2.type_ == "end5":
920
921
922
            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 )
923
    def _get_num_beads(self, contour, max_basepairs_per_bead, max_nucleotides_per_bead):
924
925
        # 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)
cmaffeo2's avatar
cmaffeo2 committed
926

927
928
    def _generate_one_bead(self, contour_position, nts):
        pos = self.contour_to_position(contour_position)
cmaffeo2's avatar
cmaffeo2 committed
929
        if self.local_twist:
930
            orientation = self.contour_to_orientation(contour_position)
cmaffeo2's avatar
cmaffeo2 committed
931
932
933
            if orientation is None:
                print("WARNING: local_twist is True, but orientation is None; using identity")
                orientation = np.eye(3)
cmaffeo2's avatar
cmaffeo2 committed
934
            opos = pos + orientation.dot( np.array((Segment.orientation_bond.r0,0,0)) )
cmaffeo2's avatar
cmaffeo2 committed
935
936
937
938
939
            # 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,
940
                                 num_nt=nts, parent=self )
941
            bead = SegmentParticle( Segment.dsDNA_particle, pos, name="DNA",
942
                                    num_nt=nts, parent=self, 
943
944
                                    orientation_bead=o,
                                    contour_position=contour_position )
cmaffeo2's avatar
cmaffeo2 committed
945
946

        else:
947
            bead = SegmentParticle( Segment.dsDNA_particle, pos, name="DNA",
948
                                    num_nt=nts, parent=self,
949
950
                                    contour_position=contour_position )
        self._add_bead(bead)
cmaffeo2's avatar
cmaffeo2 committed
951
        return bead
952
953
954
955
956
957

class SingleStrandedSegment(Segment):

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

958
    def __init__(self, name, num_nt, start_position = None,
959
960
961
                 end_position = None, 
                 segment_model = None):

cmaffeo2's avatar
cmaffeo2 committed
962
        if start_position is None: start_position = np.array((0,0,0))
963
        self.distance_per_nt = 5
964
        Segment.__init__(self, name, num_nt, 
965
966
967
968
                         start_position,
                         end_position, 
                         segment_model)

969
        self.start = self.start5 = Location( self, address=0, type_= "end5" ) # TODO change type_?
970
        self.end = self.end3 = Location( self, address=1, type_ = "end3" )