File size: 40,896 Bytes
b7731cd
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
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
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
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
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
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
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
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
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
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
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
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
956
957
958
959
960
961
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
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
1022
1023
1024
1025
1026
1027
1028
1029
1030
1031
1032
1033
1034
1035
1036
1037
1038
1039
1040
1041
1042
1043
1044
1045
1046
1047
1048
1049
1050
1051
1052
1053
1054
1055
1056
1057
1058
1059
1060
1061
1062
1063
1064
1065
1066
1067
1068
1069
1070
1071
1072
1073
1074
1075
1076
1077
1078
1079
1080
1081
1082
1083
1084
1085
1086
1087
1088
1089
1090
1091
1092
1093
1094
1095
1096
1097
1098
1099
1100
1101
1102
1103
1104
1105
1106
1107
1108
1109
1110
1111
1112
1113
1114
1115
1116
1117
1118
1119
1120
1121
1122
1123
1124
# Copyright 2019-2022 by Robert T. Miller.  All rights reserved.
# This file is part of the Biopython distribution and governed by your
# choice of the "Biopython License Agreement" or the "BSD 3-Clause License".
# Please see the LICENSE file that should have been included as part of this
# package.

"""PICIO: read and write Protein Internal Coordinate (.pic) data files."""

import re
from datetime import date
from io import StringIO

try:
    import numpy
except ImportError:
    from Bio import MissingPythonDependencyError

    raise MissingPythonDependencyError(
        "Install NumPy to build proteins from internal coordinates."
    )

from Bio.File import as_handle
from Bio.PDB.StructureBuilder import StructureBuilder
from Bio.PDB.parse_pdb_header import _parse_pdb_header_list
from Bio.PDB.PDBExceptions import PDBException

from Bio.Data.PDBData import protein_letters_1to3

from Bio.PDB.internal_coords import (
    IC_Residue,
    IC_Chain,
    Edron,
    Hedron,
    Dihedron,
    AtomKey,
)

from Bio.PDB.ic_data import (
    ic_data_backbone,
    ic_data_sidechains,
    hedra_defaults,
    dihedra_primary_defaults,
    dihedra_secondary_defaults,
    dihedra_secondary_xoxt_defaults,
)

from typing import TextIO, Set, List, Tuple, Union, Optional
from Bio.PDB.Structure import Structure
from Bio.PDB.Residue import Residue
from Bio import SeqIO


# @profile
def read_PIC(
    file: TextIO,
    verbose: bool = False,
    quick: bool = False,
    defaults: bool = False,
) -> Structure:
    """Load Protein Internal Coordinate (.pic) data from file.

    PIC file format:
        - comment lines start with #
        - (optional) PDB HEADER record
           - idcode and deposition date recommended but optional
           - deposition date in PDB format or as changed by Biopython
        - (optional) PDB TITLE record
        - repeat:
           - Biopython Residue Full ID - sets residue IDs of returned structure
           - (optional) PDB N, CA, C ATOM records for chain start
           - (optional) PIC Hedra records for residue
           - (optional) PIC Dihedra records for residue
           - (optional) BFAC records listing AtomKeys and b-factors

    An improvement would define relative positions for HOH (water) entries.

    Defaults will be supplied for any value if defaults=True.  Default values
    are supplied in ic_data.py, but structures degrade quickly with any
    deviation from true coordinates.  Experiment with
    :data:`Bio.PDB.internal_coords.IC_Residue.pic_flags` options to
    :func:`write_PIC` to verify this.

    N.B. dihedron (i-1)C-N-CA-CB is ignored in assembly if O exists.

    C-beta is by default placed using O-C-CA-CB, but O is missing
    in some PDB file residues, which means the sidechain cannot be
    placed.  The alternate CB path (i-1)C-N-CA-CB is provided to
    circumvent this, but if this is needed then it must be adjusted in
    conjunction with PHI ((i-1)C-N-CA-C) as they overlap (see :meth:`.bond_set`
    and :meth:`.bond_rotate` to handle this automatically).

    :param Bio.File file: :func:`.as_handle` file name or handle
    :param bool verbose: complain when lines not as expected
    :param bool quick: don't check residues for all dihedra (no default values)
    :param bool defaults: create di/hedra as needed from reference database.
        Amide proton created if 'H' is in IC_Residue.accept_atoms
    :returns: Biopython Structure object, Residues with .internal_coord
        attributes but no coordinates except for chain start N, CA, C atoms if
        supplied, **OR** None on parse fail (silent unless verbose=True)

    """
    proton = "H" in IC_Residue.accept_atoms

    pdb_hdr_re = re.compile(
        r"^HEADER\s{4}(?P<cf>.{1,40})"
        r"(?:\s+(?P<dd>\d\d\d\d-\d\d-\d\d|\d\d-\w\w\w-\d\d))?"
        r"(?:\s+(?P<id>[0-9A-Z]{4}))?\s*$"
    )
    pdb_ttl_re = re.compile(r"^TITLE\s{5}(?P<ttl>.+)\s*$")
    biop_id_re = re.compile(
        r"^\('(?P<pid>[^\s]*)',\s(?P<mdl>\d+),\s"
        r"'(?P<chn>\s|\w)',\s\('(?P<het>\s|[\w\s-]+)"
        r"',\s(?P<pos>-?\d+),\s'(?P<icode>\s|\w)'\)\)"
        r"\s+(?P<res>[\w]{1,3})"
        r"(\s\[(?P<segid>[a-zA-z\s]+)\])?"
        r"\s*$"
    )
    pdb_atm_re = re.compile(
        r"^ATOM\s\s(?:\s*(?P<ser>\d+))\s(?P<atm>[\w\s]{4})"
        r"(?P<alc>\w|\s)(?P<res>[\w]{3})\s(?P<chn>.)"
        r"(?P<pos>[\s\-\d]{4})(?P<icode>[A-Za-z\s])\s\s\s"
        r"(?P<x>[\s\-\d\.]{8})(?P<y>[\s\-\d\.]{8})"
        r"(?P<z>[\s\-\d\.]{8})(?P<occ>[\s\d\.]{6})"
        r"(?P<tfac>[\s\d\.]{6})\s{6}"
        r"(?P<segid>[a-zA-z\s]{4})(?P<elm>.{2})"
        r"(?P<chg>.{2})?\s*$"
    )
    pdbx_atm_re = re.compile(
        r"^ATOM\s\s(?:\s*(?P<ser>\d+))\s(?P<atm>[\w\s]{4})"
        r"(?P<alc>\w|\s)(?P<res>[\w]{3})\s(?P<chn>.)"
        r"(?P<pos>[\s\-\d]{4})(?P<icode>[A-Za-z\s])\s\s\s"
        r"(?P<x>[\s\-\d\.]{10})(?P<y>[\s\-\d\.]{10})"
        r"(?P<z>[\s\-\d\.]{10})(?P<occ>[\s\d\.]{7})"
        r"(?P<tfac>[\s\d\.]{6})\s{6}"
        r"(?P<segid>[a-zA-z\s]{4})(?P<elm>.{2})"
        r"(?P<chg>.{2})?\s*$"
    )
    bfac_re = re.compile(
        r"^BFAC:\s([^\s]+\s+[\-\d\.]+)"
        r"\s*([^\s]+\s+[\-\d\.]+)?"
        r"\s*([^\s]+\s+[\-\d\.]+)?"
        r"\s*([^\s]+\s+[\-\d\.]+)?"
        r"\s*([^\s]+\s+[\-\d\.]+)?"
    )
    bfac2_re = re.compile(r"([^\s]+)\s+([\-\d\.]+)")
    struct_builder = StructureBuilder()

    # init empty header dict
    # - could use to parse HEADER and TITLE lines except
    #   deposition_date format changed from original PDB header
    header_dict = _parse_pdb_header_list([])

    curr_SMCS = [None, None, None, None]  # struct model chain seg
    SMCS_init = [
        struct_builder.init_structure,
        struct_builder.init_model,
        struct_builder.init_chain,
        struct_builder.init_seg,
    ]

    sb_res = None
    rkl = None
    sb_chain = None
    sbcic = None
    sbric = None

    akc = {}
    hl12 = {}
    ha = {}
    hl23 = {}
    da = {}
    bfacs = {}

    orphan_aks = set()  # []

    tr = []  # this residue
    pr = []  # previous residue

    def akcache(akstr: str) -> AtomKey:
        """Maintain dictionary of AtomKeys seen while reading this PIC file."""
        # akstr: full AtomKey string read from .pic file, includes residue info
        try:
            return akc[akstr]
        except (KeyError):
            ak = akc[akstr] = AtomKey(akstr)
            return ak

    def link_residues(ppr: List[Residue], pr: List[Residue]) -> None:
        """Set next and prev links between i-1 and i-2 residues."""
        for p_r in pr:
            pric = p_r.internal_coord
            for p_p_r in ppr:
                ppric = p_p_r.internal_coord
                if p_r.id[0] == " ":  # not heteroatoms
                    if pric not in ppric.rnext:
                        ppric.rnext.append(pric)
                if p_p_r.id[0] == " ":
                    if ppric not in pric.rprev:
                        pric.rprev.append(ppric)

    def process_hedron(
        a1: str,
        a2: str,
        a3: str,
        l12: str,
        ang: str,
        l23: str,
        ric: IC_Residue,
    ) -> Tuple:
        """Create Hedron on current (sbcic) Chain.internal_coord."""
        ek = (akcache(a1), akcache(a2), akcache(a3))
        atmNdx = AtomKey.fields.atm
        accpt = IC_Residue.accept_atoms
        if not all(ek[i].akl[atmNdx] in accpt for i in range(3)):
            return
        hl12[ek] = float(l12)
        ha[ek] = float(ang)
        hl23[ek] = float(l23)
        sbcic.hedra[ek] = ric.hedra[ek] = h = Hedron(ek)
        h.cic = sbcic
        ak_add(ek, ric)
        return ek

    def default_hedron(ek: Tuple, ric: IC_Residue) -> None:
        """Create Hedron based on same re_class hedra in ref database.

        Adds Hedron to current Chain.internal_coord, see ic_data for default
        values and reference database source.
        """
        atomkeys = []
        hkey = None

        atmNdx = AtomKey.fields.atm
        resNdx = AtomKey.fields.resname
        resPos = AtomKey.fields.respos
        atomkeys = [ek[i].akl for i in range(3)]

        atpl = tuple([atomkeys[i][atmNdx] for i in range(3)])
        res = atomkeys[0][resNdx]

        if (
            atomkeys[0][resPos]
            != atomkeys[2][resPos]  # hedra crosses amide bond so not reversed
            or atpl == ("N", "CA", "C")  # or chain start tau
            or atpl in ic_data_backbone  # or found forward hedron in ic_data
            or (res not in ["A", "G"] and atpl in ic_data_sidechains[res])
        ):
            hkey = ek
            rhcl = [atomkeys[i][resNdx] + atomkeys[i][atmNdx] for i in range(3)]
            try:
                dflts = hedra_defaults["".join(rhcl)][0]
            except KeyError:
                if atomkeys[0][resPos] == atomkeys[1][resPos]:
                    rhcl = [atomkeys[i][resNdx] + atomkeys[i][atmNdx] for i in range(2)]
                    rhc = "".join(rhcl) + "X" + atomkeys[2][atmNdx]
                else:
                    rhcl = [
                        atomkeys[i][resNdx] + atomkeys[i][atmNdx] for i in range(1, 3)
                    ]
                    rhc = "X" + atomkeys[0][atmNdx] + "".join(rhcl)
                dflts = hedra_defaults[rhc][0]
        else:
            # must be reversed or fail
            hkey = ek[::-1]
            rhcl = [atomkeys[i][resNdx] + atomkeys[i][atmNdx] for i in range(2, -1, -1)]
            dflts = hedra_defaults["".join(rhcl)][0]

        process_hedron(
            str(hkey[0]),
            str(hkey[1]),
            str(hkey[2]),
            dflts[0],
            dflts[1],
            dflts[2],
            ric,
        )

        if verbose:
            print(f" default for {ek}")

    def hedra_check(dk: Tuple, ric: IC_Residue) -> None:
        """Confirm both hedra present for dihedron key, use default if set."""
        if dk[0:3] not in sbcic.hedra and dk[2::-1] not in sbcic.hedra:
            if defaults:
                default_hedron(dk[0:3], ric)
            else:
                print(f"{dk} missing h1")
        if dk[1:4] not in sbcic.hedra and dk[3:0:-1] not in sbcic.hedra:
            if defaults:
                default_hedron(dk[1:4], ric)
            else:
                print(f"{dk} missing h2")

    def process_dihedron(
        a1: str, a2: str, a3: str, a4: str, dangle: str, ric: IC_Residue
    ) -> Set:
        """Create Dihedron on current Chain.internal_coord."""
        ek = (
            akcache(a1),
            akcache(a2),
            akcache(a3),
            akcache(a4),
        )
        atmNdx = AtomKey.fields.atm
        accpt = IC_Residue.accept_atoms
        if not all(ek[i].akl[atmNdx] in accpt for i in range(4)):
            return
        da[ek] = float(dangle)
        sbcic.dihedra[ek] = ric.dihedra[ek] = d = Dihedron(ek)
        d.cic = sbcic
        if not quick:
            hedra_check(ek, ric)
        ak_add(ek, ric)
        return ek

    def default_dihedron(ek: List, ric: IC_Residue) -> None:
        """Create Dihedron based on same residue class dihedra in ref database.

        Adds Dihedron to current Chain.internal_coord, see ic_data for default
        values and reference database source.
        """
        atmNdx = AtomKey.fields.atm
        resNdx = AtomKey.fields.resname
        resPos = AtomKey.fields.respos

        rdclass = ""
        dclass = ""
        for ak in ek:
            dclass += ak.akl[atmNdx]
            rdclass += ak.akl[resNdx] + ak.akl[atmNdx]
        if dclass == "NCACN":
            rdclass = rdclass[0:7] + "XN"
        elif dclass == "CACNCA":
            rdclass = "XCAXC" + rdclass[5:]
        elif dclass == "CNCAC":
            rdclass = "XC" + rdclass[2:]
        if rdclass in dihedra_primary_defaults:
            process_dihedron(
                str(ek[0]),
                str(ek[1]),
                str(ek[2]),
                str(ek[3]),
                dihedra_primary_defaults[rdclass][0],
                ric,
            )

            if verbose:
                print(f" default for {ek}")

        elif rdclass in dihedra_secondary_defaults:
            primAngle, offset = dihedra_secondary_defaults[rdclass]
            rname = ek[2].akl[resNdx]
            rnum = int(ek[2].akl[resPos])
            paKey = None
            if primAngle == ("N", "CA", "C", "N") and ek[0].ric.rnext != []:
                paKey = [
                    AtomKey((rnum, None, rname, primAngle[x], None, None))
                    for x in range(3)
                ]
                rnext = ek[0].ric.rnext
                paKey.append(
                    AtomKey(
                        (
                            rnext[0].rbase[0],
                            None,
                            rnext[0].rbase[2],
                            "N",
                            None,
                            None,
                        )
                    )
                )
                paKey = tuple(paKey)
            elif primAngle == ("CA", "C", "N", "CA"):
                prname = pr.akl[0][resNdx]
                prnum = pr.akl[0][resPos]
                paKey = [
                    AtomKey(prnum, None, prname, primAngle[x], None, None)
                    for x in range(0, 2)
                ]
                paKey.add(
                    [
                        AtomKey((rnum, None, rname, primAngle[x], None, None))
                        for x in range(2, 4)
                    ]
                )
                paKey = tuple(paKey)
            else:
                paKey = tuple(
                    AtomKey((rnum, None, rname, atm, None, None)) for atm in primAngle
                )

            if paKey in da:
                process_dihedron(
                    str(ek[0]),
                    str(ek[1]),
                    str(ek[2]),
                    str(ek[3]),
                    da[paKey] + dihedra_secondary_defaults[rdclass][1],
                    ric,
                )

                if verbose:
                    print(f" secondary default for {ek}")

            elif rdclass in dihedra_secondary_xoxt_defaults:
                if primAngle == ("C", "N", "CA", "C"):  # primary for alt cb
                    # no way to trigger alt cb with default=True
                    # because will generate default N-CA-C-O
                    prname = pr.akl[0][resNdx]
                    prnum = pr.akl[0][resPos]
                    paKey = [AtomKey(prnum, None, prname, primAngle[0], None, None)]
                    paKey.add(
                        [
                            AtomKey((rnum, None, rname, primAngle[x], None, None))
                            for x in range(1, 4)
                        ]
                    )
                    paKey = tuple(paKey)
                else:
                    primAngle, offset = dihedra_secondary_xoxt_defaults[rdclass]
                    rname = ek[2].akl[resNdx]
                    rnum = int(ek[2].akl[resPos])
                    paKey = tuple(
                        AtomKey((rnum, None, rname, atm, None, None))
                        for atm in primAngle
                    )

                if paKey in da:
                    process_dihedron(
                        str(ek[0]),
                        str(ek[1]),
                        str(ek[2]),
                        str(ek[3]),
                        da[paKey] + offset,
                        ric,
                    )

                    if verbose:
                        print(f" oxt default for {ek}")

                else:
                    print(
                        f"missing primary angle {paKey} {primAngle} to "
                        f"generate {rnum}{rname} {rdclass}"
                    )
        else:
            print(
                f"missing {ek} -> {rdclass} ({dclass}) not found in primary or"
                " secondary defaults"
            )

    def dihedra_check(ric: IC_Residue) -> None:
        """Look for required dihedra in residue, generate defaults if set."""
        # rnext should be set
        def ake_recurse(akList: List) -> List:
            """Bulid combinatorics of AtomKey lists."""
            car = akList[0]
            if len(akList) > 1:
                retList = []
                for ak in car:
                    cdr = akList[1:]
                    rslt = ake_recurse(cdr)
                    for r in rslt:
                        r.insert(0, ak)
                        retList.append(r)
                return retList
            else:
                if len(car) == 1:
                    return [list(car)]
                else:
                    retList = [[ak] for ak in car]
                    return retList

        def ak_expand(eLst: List) -> List:
            """Expand AtomKey list with altlocs, all combinatorics."""
            retList = []
            for edron in eLst:
                newList = []
                for ak in edron:
                    rslt = ak.ric.split_akl([ak])
                    rlst = [r[0] for r in rslt]
                    if rlst != []:
                        newList.append(rlst)
                    else:
                        newList.append([ak])
                rslt = ake_recurse(newList)
                for r in rslt:
                    retList.append(r)
            return retList

        # dihedra_check processing starts here
        # generate the list of dihedra this residue should have
        chkLst = []
        sN, sCA, sC = AtomKey(ric, "N"), AtomKey(ric, "CA"), AtomKey(ric, "C")
        sO, sCB, sH = AtomKey(ric, "O"), AtomKey(ric, "CB"), AtomKey(ric, "H")
        if ric.rnext != []:
            for rn in ric.rnext:
                nN, nCA, nC = (
                    AtomKey(rn, "N"),
                    AtomKey(rn, "CA"),
                    AtomKey(rn, "C"),
                )
                # intermediate residue, need psi, phi, omg
                chkLst.append((sN, sCA, sC, nN))  # psi
                chkLst.append((sCA, sC, nN, nCA))  # omg i+1
                chkLst.append((sC, nN, nCA, nC))  # phi i+1
        else:
            chkLst.append((sN, sCA, sC, AtomKey(ric, "OXT")))  # psi
            rn = "(no rnext)"

        chkLst.append((sN, sCA, sC, sO))  # locate backbone O
        if ric.lc != "G":
            chkLst.append((sO, sC, sCA, sCB))  # locate CB
            if ric.lc == "A":
                chkLst.append((sN, sCA, sCB))  # missed for generate from seq
        if ric.rprev != [] and ric.lc != "P" and proton:
            chkLst.append((sC, sCA, sN, sH))  # amide proton

        try:
            for edron in ic_data_sidechains[ric.lc]:
                if len(edron) > 3:  # dihedra only
                    if all(not atm[0] == "H" for atm in edron):
                        akl = [AtomKey(ric, atm) for atm in edron[0:4]]
                        chkLst.append(akl)
        except KeyError:
            pass

        # now compare generated list to ric.dihedra, get defaults if set.
        chkLst = ak_expand(chkLst)
        altloc_ndx = AtomKey.fields.altloc

        for dk in chkLst:
            if tuple(dk) in ric.dihedra:
                pass
            elif sH in dk:
                pass  # ignore missing hydrogens
            elif all(atm.akl[altloc_ndx] is None for atm in dk):
                if defaults:
                    if len(dk) != 3:
                        default_dihedron(dk, ric)
                    else:
                        default_hedron(dk, ric)  # add ALA N-Ca-Cb
                else:
                    if verbose:
                        print(f"{ric}-{rn} missing {dk}")
            else:
                # print(f"skip {ek}")
                pass  # ignore missing combinatoric of altloc atoms
                # need more here?

    def ak_add(ek: Tuple, ric: IC_Residue) -> None:
        """Allocate edron key AtomKeys to current residue as appropriate.

        A hedron or dihedron may span a backbone amide bond, this routine
        allocates atoms in the (h/di)edron to the ric residue or saves them
        for a residue yet to be processed.

        :param set ek: AtomKeys in edron
        :param IC_Residue ric: current residue to assign AtomKeys to
        """
        res = ric.residue
        reskl = (
            str(res.id[1]),
            (None if res.id[2] == " " else res.id[2]),
            ric.lc,
        )
        for ak in ek:
            if ak.ric is None:
                sbcic.akset.add(ak)
                if ak.akl[0:3] == reskl:
                    ak.ric = ric
                    ric.ak_set.add(ak)
                else:
                    orphan_aks.add(ak)

    def finish_chain() -> None:
        """Do last rnext, rprev links and process chain edra data."""
        link_residues(pr, tr)
        # check/confirm completeness
        if not quick:
            for r in pr:
                dihedra_check(r.internal_coord)
            for r in tr:
                dihedra_check(r.internal_coord)

        if ha != {}:
            sha = {k: ha[k] for k in sorted(ha)}
            shl12 = {k: hl12[k] for k in sorted(hl12)}
            shl23 = {k: hl23[k] for k in sorted(hl23)}
            sbcic._hedraDict2chain(shl12, sha, shl23, da, bfacs)

    # read_PIC processing starts here:
    with as_handle(file, mode="r") as handle:
        for line in handle.readlines():
            if line.startswith("#"):
                pass  # skip comment lines
            elif line.startswith("HEADER "):
                m = pdb_hdr_re.match(line)
                if m:
                    header_dict["head"] = m.group("cf")  # classification
                    header_dict["idcode"] = m.group("id")
                    header_dict["deposition_date"] = m.group("dd")
                elif verbose:
                    print("Reading pic file", file, "HEADER parse fail: ", line)
            elif line.startswith("TITLE "):
                m = pdb_ttl_re.match(line)
                if m:
                    header_dict["name"] = m.group("ttl").strip()
                    # print('TTL: ', m.group('ttl').strip())
                elif verbose:
                    print("Reading pic file", file, "TITLE parse fail:, ", line)
            elif line.startswith("("):  # Biopython ID line for Residue
                m = biop_id_re.match(line)
                if m:
                    # check SMCS = Structure, Model, Chain, SegID
                    segid = m.group(9)
                    if segid is None:
                        segid = "    "
                    this_SMCS = [
                        m.group(1),
                        int(m.group(2)),
                        m.group(3),
                        segid,
                    ]
                    if curr_SMCS != this_SMCS:
                        if curr_SMCS[:3] != this_SMCS[:3] and ha != {}:
                            # chain change so process current chain data
                            finish_chain()

                            akc = {}  # atomkey cache, used by akcache()
                            hl12 = {}  # hedra key -> len12
                            ha = {}  # -> hedra angle
                            hl23 = {}  # -> len23
                            da = {}  # dihedra key -> angle value
                            bfacs = {}  # atomkey string -> b-factor
                        # init new Biopython SMCS level as needed
                        for i in range(4):
                            if curr_SMCS[i] != this_SMCS[i]:
                                SMCS_init[i](this_SMCS[i])
                                curr_SMCS[i] = this_SMCS[i]
                                if i == 0:
                                    # 0 = init structure so add header
                                    struct_builder.set_header(header_dict)
                                elif i == 1:
                                    # new model means new chain and new segid
                                    curr_SMCS[2] = curr_SMCS[3] = None
                                elif i == 2:
                                    # new chain so init internal_coord
                                    sb_chain = struct_builder.chain
                                    sbcic = sb_chain.internal_coord = IC_Chain(sb_chain)

                    struct_builder.init_residue(
                        m.group("res"),
                        m.group("het"),
                        int(m.group("pos")),
                        m.group("icode"),
                    )

                    sb_res = struct_builder.residue
                    if sb_res.id[0] != " ":  # skip hetatm
                        continue
                    if 2 == sb_res.is_disordered():
                        for r in sb_res.child_dict.values():
                            if not r.internal_coord:
                                sb_res = r
                                break
                        # added to disordered res
                        tr.append(sb_res)
                    else:
                        # new res so fix up previous residue as feasible
                        link_residues(pr, tr)

                        if not quick:
                            for r in pr:
                                # create di/hedra if default for residue i-1
                                # just linked
                                dihedra_check(r.internal_coord)

                        pr = tr
                        tr = [sb_res]

                    sbric = sb_res.internal_coord = IC_Residue(
                        sb_res
                    )  # no atoms so no rak
                    sbric.cic = sbcic
                    rkl = (
                        str(sb_res.id[1]),
                        (None if sb_res.id[2] == " " else sb_res.id[2]),
                        sbric.lc,
                    )
                    sbcic.ordered_aa_ic_list.append(sbric)

                    # update AtomKeys w/o IC_Residue references, in case
                    # chain ends before di/hedra sees them (2XHE test case)
                    for ak in orphan_aks:
                        if ak.akl[0:3] == rkl:
                            ak.ric = sbric
                            sbric.ak_set.add(ak)
                            # may need altoc support here
                    orphan_aks = set(filter(lambda ak: ak.ric is None, orphan_aks))

                else:
                    if verbose:
                        print(
                            "Reading pic file",
                            file,
                            "residue ID parse fail: ",
                            line,
                        )
                    return None
            elif line.startswith("ATOM "):
                m = pdb_atm_re.match(line)
                if not m:
                    m = pdbx_atm_re.match(line)
                if m:
                    if sb_res is None:
                        # ATOM without res spec already loaded, not a pic file
                        if verbose:
                            print(
                                "Reading pic file",
                                file,
                                "ATOM without residue configured:, ",
                                line,
                            )
                        return None
                    if sb_res.resname != m.group("res") or sb_res.id[1] != int(
                        m.group("pos")
                    ):
                        if verbose:
                            print(
                                "Reading pic file",
                                file,
                                "ATOM not in configured residue (",
                                sb_res.resname,
                                str(sb_res.id),
                                "):",
                                line,
                            )
                        return None
                    coord = numpy.array(
                        (
                            float(m.group("x")),
                            float(m.group("y")),
                            float(m.group("z")),
                        ),
                        "f",
                    )
                    struct_builder.init_atom(
                        m.group("atm").strip(),
                        coord,
                        float(m.group("tfac")),
                        float(m.group("occ")),
                        m.group("alc"),
                        m.group("atm"),
                        int(m.group("ser")),
                        m.group("elm").strip(),
                    )

                    # reset because prev does not link to this residue
                    # (chainBreak)
                    pr = []

            elif line.startswith("BFAC: "):
                m = bfac_re.match(line)
                if m:
                    for bfac_pair in m.groups():
                        if bfac_pair is not None:
                            m2 = bfac2_re.match(bfac_pair)
                            bfacs[m2.group(1)] = float(m2.group(2))
                # else:
                #    print f"Reading pic file {file} B-factor fail: {line}"
            else:
                m = Edron.edron_re.match(line)
                if m and sb_res is not None:
                    if m["a4"] is None:
                        process_hedron(
                            m["a1"],
                            m["a2"],
                            m["a3"],
                            m["len12"],
                            m["angle"],
                            m["len23"],
                            sb_res.internal_coord,
                        )
                    else:
                        process_dihedron(
                            m["a1"],
                            m["a2"],
                            m["a3"],
                            m["a4"],
                            m["dihedral"],
                            sb_res.internal_coord,
                        )

                elif m:
                    print(
                        "PIC file: ",
                        file,
                        " error: no residue info before reading (di/h)edron: ",
                        line,
                    )
                    return None
                elif line.strip():
                    if verbose:
                        print(
                            "Reading PIC file",
                            file,
                            "parse fail on: .",
                            line,
                            ".",
                        )
                    return None

    # reached end of input
    finish_chain()

    # print(report_PIC(struct_builder.get_structure()))
    return struct_builder.get_structure()


def read_PIC_seq(
    seqRec: "SeqIO.SeqRecord",
    pdbid: str = None,
    title: str = None,
    chain: str = None,
) -> Structure:
    """Read :class:`.SeqRecord` into Structure with default internal coords."""
    read_pdbid, read_title, read_chain = None, None, None

    if seqRec.id is not None:
        read_pdbid = seqRec.id
    if seqRec.description is not None:
        read_title = seqRec.description.replace(f"{read_pdbid} ", "")
    if ":" in read_pdbid:
        read_pdbid, read_chain = read_pdbid.split(":")

    if chain is None:
        chain = read_chain if read_chain is not None else "A"
    if title is None:
        title = (
            read_title
            if read_title is not None
            else f"sequence input {seqRec.id if seqRec.id is not None else ''}"
        )
    if pdbid is None:
        pdbid = read_pdbid if read_pdbid is not None else "0PDB"

    today = date.today()
    datestr = (today.strftime("%d-%b-%y")).upper()
    output = f"HEADER    {'GENERATED STRUCTURE':40}{datestr}   {pdbid}\n"
    output += f"TITLE     {title.upper():69}\n"

    ndx = 1
    for r in seqRec.seq:
        output += (
            f"('{pdbid}', 0, '{chain}', (' ', {ndx}, ' ')) {protein_letters_1to3[r]}\n"
        )
        ndx += 1

    sp = StringIO()
    sp.write(output)
    sp.seek(0)
    return read_PIC(sp, defaults=True)


def _wpr(
    entity,
    fp,
    pdbid,
    chainid,
    picFlags: int = IC_Residue.picFlagsDefault,
    hCut: Optional[Union[float, None]] = None,
    pCut: Optional[Union[float, None]] = None,
):
    if entity.internal_coord:
        if not chainid or not pdbid:
            chain = entity.parent
            if not chainid:
                chainid = chain.id
            if not pdbid:
                struct = chain.parent.parent
                pdbid = struct.header.get("idcode")

        fp.write(
            entity.internal_coord._write_PIC(
                pdbid, chainid, picFlags=picFlags, hCut=hCut, pCut=pCut
            )
        )
    else:
        fp.write(IC_Residue._residue_string(entity))


def _enumerate_entity_atoms(entity):
    need = False
    for atm in entity.get_atoms():
        need = not atm.get_serial_number()
        break
    if need:
        anum = 1
        for res in entity.get_residues():
            if 2 == res.is_disordered():
                for r in res.child_dict.values():
                    for atm in r.get_unpacked_list():
                        atm.set_serial_number(anum)
                        anum += 1
            else:
                for atm in res.get_unpacked_list():
                    atm.set_serial_number(anum)
                    anum += 1


def enumerate_atoms(entity):
    """Ensure all atoms in entity have serial_number set."""
    while entity.get_parent():
        entity = entity.get_parent()  # get to top level

    if "S" == entity.level:
        for mdl in entity:  # each model starts with 1
            _enumerate_entity_atoms(mdl)
    else:  # only Chain or Residue, start with 1
        _enumerate_entity_atoms(entity)


def pdb_date(datestr: str) -> str:
    """Convert yyyy-mm-dd date to dd-month-yy."""
    if datestr:
        m = re.match(r"(\d{4})-(\d{2})-(\d{2})", datestr)
        if m:
            mo = [
                "XXX",
                "JAN",
                "FEB",
                "MAR",
                "APR",
                "MAY",
                "JUN",
                "JUL",
                "AUG",
                "SEP",
                "OCT",
                "NOV",
                "DEC",
            ][int(m.group(2))]
            datestr = m.group(3) + "-" + mo + "-" + m.group(1)[-2:]
    return datestr


def write_PIC(
    entity,
    file,
    pdbid=None,
    chainid=None,
    picFlags: int = IC_Residue.picFlagsDefault,
    hCut: Optional[Union[float, None]] = None,
    pCut: Optional[Union[float, None]] = None,
):
    """Write Protein Internal Coordinates (PIC) to file.

    See :func:`read_PIC` for file format.
    See :data:`IC_Residue.pic_accuracy` to vary numeric accuracy.
    Recurses to lower entity levels (M, C, R).

    :param Entity entity: Biopython PDB Entity object: S, M, C or R
    :param Bio.File file: :func:`.as_handle` file name or handle
    :param str pdbid: PDB idcode, read from entity if not supplied
    :param char chainid: PDB Chain ID, set from C level entity.id if needed
    :param int picFlags: boolean flags controlling output, defined in
        :data:`Bio.PDB.internal_coords.IC_Residue.pic_flags`

        * "psi",
        * "omg",
        * "phi",
        * "tau",  # tau hedron (N-Ca-C)
        * "chi1",
        * "chi2",
        * "chi3",
        * "chi4",
        * "chi5",
        * "pomg",  # proline omega
        * "chi",   # chi1 through chi5
        * "classic_b",  # psi | phi | tau | pomg
        * "classic",    # classic_b | chi
        * "hedra",      # all hedra including bond lengths
        * "primary",    # all primary dihedra
        * "secondary",  # all secondary dihedra (fixed angle from primary dihedra)
        * "all",        # hedra | primary | secondary
        * "initAtoms",  # XYZ coordinates of initial Tau (N-Ca-C)
        * "bFactors"

        default is everything::

            picFlagsDefault = (
                pic_flags.all | pic_flags.initAtoms | pic_flags.bFactors
            )

        Usage in your code::

            # just primary dihedra and all hedra
            picFlags = (
                IC_Residue.pic_flags.primary | IC_Residue.pic_flags.hedra
            )

            # no B-factors:
            picFlags = IC_Residue.picFlagsDefault
            picFlags &= ~IC_Residue.pic_flags.bFactors

        :func:`read_PIC` with `(defaults=True)` will use default values for
        anything left out

    :param float hCut: default None
        only write hedra with ref db angle std dev greater than this value
    :param float pCut: default None
        only write primary dihedra with ref db angle std dev greater than this
        value

    **Default values**:

    Data averaged from Sep 2019 Dunbrack cullpdb_pc20_res2.2_R1.0.

    Please see

    `PISCES: A Protein Sequence Culling Server <https://dunbrack.fccc.edu/pisces/>`_

    'G. Wang and R. L. Dunbrack, Jr. PISCES: a protein sequence culling
    server. Bioinformatics, 19:1589-1591, 2003.'

    'primary' and 'secondary' dihedra are defined in ic_data.py.  Specifically,
    secondary dihedra can be determined as a fixed rotation from another known
    angle, for example N-Ca-C-O can be estimated from N-Ca-C-N (psi).

    Standard deviations are listed in
    <biopython distribution>/Bio/PDB/ic_data.py for default values, and can be
    used to limit which hedra and dihedra are defaulted vs. output exact
    measurements from structure (see hCut and pCut above).  Default values for
    primary dihedra (psi, phi, omega, chi1, etc.) are chosen as the most common
    integer value, not an average.

    :raises PDBException: if entity level is A (Atom)
    :raises Exception: if entity does not have .level attribute
    """
    enumerate_atoms(entity)

    with as_handle(file, "w") as fp:
        try:
            if "A" == entity.level:
                raise PDBException("No PIC output at Atom level")
            elif "R" == entity.level:
                if 2 == entity.is_disordered():
                    for r in entity.child_dict.values():
                        _wpr(
                            r,
                            fp,
                            pdbid,
                            chainid,
                            picFlags=picFlags,
                            hCut=hCut,
                            pCut=pCut,
                        )
                else:
                    _wpr(
                        entity,
                        fp,
                        pdbid,
                        chainid,
                        picFlags=picFlags,
                        hCut=hCut,
                        pCut=pCut,
                    )
            elif "C" == entity.level:
                if not chainid:
                    chainid = entity.id
                for res in entity:
                    write_PIC(
                        res,
                        fp,
                        pdbid,
                        chainid,
                        picFlags=picFlags,
                        hCut=hCut,
                        pCut=pCut,
                    )
            elif "M" == entity.level:
                for chn in entity:
                    write_PIC(
                        chn,
                        fp,
                        pdbid,
                        chainid,
                        picFlags=picFlags,
                        hCut=hCut,
                        pCut=pCut,
                    )
            elif "S" == entity.level:
                if not pdbid:
                    pdbid = entity.header.get("idcode", None)
                hdr = entity.header.get("head", None)
                dd = pdb_date(entity.header.get("deposition_date", None))
                if hdr:
                    fp.write(
                        ("HEADER    {:40}{:8}   {:4}\n").format(
                            hdr.upper(), (dd or ""), (pdbid or "")
                        )
                    )
                nam = entity.header.get("name", None)
                if nam:
                    fp.write("TITLE     " + nam.upper() + "\n")
                for mdl in entity:
                    write_PIC(
                        mdl,
                        fp,
                        pdbid,
                        chainid,
                        picFlags=picFlags,
                        hCut=hCut,
                        pCut=pCut,
                    )
            else:
                raise PDBException("Cannot identify level: " + str(entity.level))
        except KeyError:
            raise Exception(
                "write_PIC: argument is not a Biopython PDB Entity " + str(entity)
            )