Гомологичное моделирование комплекса белка с лигандом
In [51]:
import sys
import modeller
import _modeller
import modeller.automodel
In [3]:
# set modeller parameters
env=modeller.environ()
env.io.hetatm=True
MODELLER 9.19, 2017/07/19, r11078
PROTEIN STRUCTURE MODELLING BY SATISFACTION OF SPATIAL RESTRAINTS
Copyright(c) 1989-2017 Andrej Sali
All Rights Reserved
Written by A. Sali
with help from
B. Webb, M.S. Madhusudhan, M-Y. Shen, G.Q. Dong,
M.A. Marti-Renom, N. Eswar, F. Alber, M. Topf, B. Oliva,
A. Fiser, R. Sanchez, B. Yerkovich, A. Badretdinov,
F. Melo, J.P. Overington, E. Feyfant
University of California, San Francisco, USA
Rockefeller University, New York, USA
Harvard University, Cambridge, USA
Imperial Cancer Research Fund, London, UK
Birkbeck College, University of London, London, UK
Kind, OS, HostName, Kernel, Processor: 4, Linux shadbox 3.2.0-29-generic x86_64
Date and time of compilation : 2017/07/19 14:40:43
MODELLER executable type : x86_64-intel8
Job starting time (YY/MM/DD HH:MM:SS): 2017/12/22 17:19:12
In [5]:
%%bash
# get protein template with known structure
wget http://www.pdb.org/pdb/files/1lmp.pdb
# get sequence of related protein with "unknown" structure (human lysozyme)
wget http://www.uniprot.org/uniprot/B2R4C5.fasta
--2017-12-22 17:27:28-- http://www.pdb.org/pdb/files/1lmp.pdb
Resolving www.pdb.org (www.pdb.org)... 128.6.244.52
Connecting to www.pdb.org (www.pdb.org)|128.6.244.52|:80... connected.
HTTP request sent, awaiting response... 301 Moved Permanently
Location: https://www.rcsb.org/pdb/files/1lmp.pdb [following]
--2017-12-22 17:27:29-- https://www.rcsb.org/pdb/files/1lmp.pdb
Resolving www.rcsb.org (www.rcsb.org)... 132.249.213.110
Connecting to www.rcsb.org (www.rcsb.org)|132.249.213.110|:443... connected.
HTTP request sent, awaiting response... 301 Moved Permanently
Location: http://files.rcsb.org/view/1lmp.pdb [following]
--2017-12-22 17:27:30-- http://files.rcsb.org/view/1lmp.pdb
Resolving files.rcsb.org (files.rcsb.org)... 132.249.213.140
Connecting to files.rcsb.org (files.rcsb.org)|132.249.213.140|:80... connected.
HTTP request sent, awaiting response... 200 OK
Length: unspecified [text/plain]
Saving to: `1lmp.pdb'
0K .......... .......... .......... .......... .......... 127K
50K .......... .......... .......... .......... .......... 248K
100K .......... .......... ........ 221K=0.7s
2017-12-22 17:27:31 (177 KB/s) - `1lmp.pdb' saved [131301]
--2017-12-22 17:27:31-- http://www.uniprot.org/uniprot/B2R4C5.fasta
Resolving www.uniprot.org (www.uniprot.org)... 193.62.193.81, 128.175.240.211
Connecting to www.uniprot.org (www.uniprot.org)|193.62.193.81|:80... connected.
HTTP request sent, awaiting response... 200 OK
Length: 217 [text/plain]
Saving to: `B2R4C5.fasta'
0K 100% 39.6M=0s
2017-12-22 17:27:33 (39.6 MB/s) - `B2R4C5.fasta' saved [217/217]
In [8]:
# create alignment object
alignment=modeller.alignment(env)
# add sequence
alignment.append(file='B2R4C5.fasta', align_codes='all',alignment_format='FASTA')
# add structure
mdl = modeller.model(env, file='1lmp.pdb', model_segment=('FIRST:'+'A', 'LAST:'+'A'))
alignment.append_model(mdl, atom_files='1lmp.pdb', align_codes='1lmp')
# align and save
alignment.salign()
alignment.write(file='all_in_one.ali', alignment_format='PIR')
SALIGN_____> adding the next group to the alignment; iteration 1
In [9]:
cat 'all_in_one.ali'
>P1;tr|B2R4C5|B2R4C5_HUMAN sequence:: : : : :::-1.00:-1.00 MKALIVLGLVLLSVTVQGKVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYNTRATNYNAGDRSTDYGIF QINSRYWCNDGKTPGAVNACHLSCSALLQDNIADAVACAKRVVRDPQGIRAWVAWRNRCQNRDVRQYVQGCGV-- -* >P1;1lmp structureX:1lmp.pdb: 1 :A:+132 :A:MOL_ID 1; MOLECULE LYSOZYME; CHAIN A; SYNONYM MUCOPEPTIDE N-ACETYLMURAMYLHYDROLASE; EC 3.2.1.17:MOL_ID 1; ORGANISM_SCIENTIFIC ONCORHYNCHUS MYKISS; ORGANISM_COMMON RAINBOW TROUT; ORGANISM_TAXID 8022; ORGAN KIDNEY: 2.00: 0.16 ------------------KVYDRCELARALKASGMDGYAGNSLPNWVCLSKWESSYNTQATNRNT-DGSTDYGIF QINSRYWCDDGRTPGAKNVCGIRCSQLLTDDLTVAIRCAKRVVLDPNGIGAWVAWRLHCQNQDLRSYVAGCGV.. .*
In [20]:
s = alignment[0]
pdb = alignment[1]
# build model
a = modeller.automodel.automodel(env, alnfile='all_in_one.ali', knowns= pdb.code, sequence = s.code )
a.name='mod'+s.code
a.starting_model = 1
a.ending_model = 1
a.make()
tr|B2R4C5|B2R4C5_HUMAN 1lmp
fndatmi_285W> Only 129 residues out of 132 contain atoms of type CA
(This is usually caused by non-standard residues, such
as ligands, or by PDB files with missing atoms.)
fndatmi_285W> Only 129 residues out of 132 contain atoms of type CA
(This is usually caused by non-standard residues, such
as ligands, or by PDB files with missing atoms.)
check_ali___> Checking the sequence-structure alignment.
Implied intrachain target CA(i)-CA(i+1) distances longer than 8.0 angstroms:
ALN_POS TMPL RID1 RID2 NAM1 NAM2 DIST
----------------------------------------------
END OF TABLE
read_to_681_> topology.submodel read from topology file: 3
fndatmi_285W> Only 129 residues out of 132 contain atoms of type CA
(This is usually caused by non-standard residues, such
as ligands, or by PDB files with missing atoms.)
patch_s_522_> Number of disulfides patched in MODEL: 4
mdtrsr__446W> A potential that relies on one protein is used, yet you have at
least one known structure available. MDT, not library, potential is used.
iup2crm_280W> No topology library in memory or assigning a BLK residue.
Default CHARMM atom type assigned: C1 --> CT2
This message is written only for the first such atom.
0 atoms in HETATM/BLK residues constrained
to protein atoms within 2.30 angstroms
and protein CA atoms within 10.00 angstroms
0 atoms in residues without defined topology
constrained to be rigid bodies
condens_443_> Restraints marked for deletion were removed.
Total number of restraints before, now: 13194 12190
iupac_m_397W> Atoms were not swapped because of the uncertainty of how to handle the H atom.
>> ENERGY; Differences between the model's features and restraints:
Number of all residues in MODEL : 148
Number of all, selected real atoms : 1157 1157
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 12190 12190
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 2338
Dynamic pairs routine : 2, NATM x NATM cell sorting
Atomic shift for contacts update (UPDATE_DYNAMIC) : 0.390
LENNARD_JONES_SWITCH : 6.500 7.500
COULOMB_JONES_SWITCH : 6.500 7.500
RESIDUE_SPAN_RANGE : 0 99999
NLOGN_USE : 15
CONTACT_SHELL : 4.000
DYNAMIC_PAIRS,_SPHERE,_COULOMB,_LENNARD,_MODELLER : T T F F F
SPHERE_STDV : 0.050
RADII_FACTOR : 0.820
Current energy : 784.9276
Summary of the restraint violations:
NUM ... number of restraints.
NUMVI ... number of restraints with RVIOL > VIOL_REPORT_CUT[i].
RVIOL ... relative difference from the best value.
NUMVP ... number of restraints with -Ln(pdf) > VIOL_REPORT_CUT2[i].
RMS_1 ... RMS(feature, minimally_violated_basis_restraint, NUMB).
RMS_2 ... RMS(feature, best_value, NUMB).
MOL.PDF ... scaled contribution to -Ln(Molecular pdf).
# RESTRAINT_GROUP NUM NUMVI NUMVP RMS_1 RMS_2 MOL.PDF S_i
------------------------------------------------------------------------------------------------------
1 Bond length potential : 1177 0 0 0.006 0.006 11.531 1.000
2 Bond angle potential : 1592 0 6 2.099 2.099 141.87 1.000
3 Stereochemical cosine torsion poten: 738 0 27 47.960 47.960 267.80 1.000
4 Stereochemical improper torsion pot: 481 0 0 1.360 1.360 19.813 1.000
5 Soft-sphere overlap restraints : 2338 0 0 0.001 0.001 0.56110 1.000
6 Lennard-Jones 6-12 potential : 0 0 0 0.000 0.000 0.0000 1.000
7 Coulomb point-point electrostatic p: 0 0 0 0.000 0.000 0.0000 1.000
8 H-bonding potential : 0 0 0 0.000 0.000 0.0000 1.000
9 Distance restraints 1 (CA-CA) : 2405 0 0 0.126 0.126 37.277 1.000
10 Distance restraints 2 (N-O) : 2564 0 0 0.152 0.152 66.586 1.000
11 Mainchain Phi dihedral restraints : 0 0 0 0.000 0.000 0.0000 1.000
12 Mainchain Psi dihedral restraints : 0 0 0 0.000 0.000 0.0000 1.000
13 Mainchain Omega dihedral restraints: 147 0 3 4.455 4.455 34.406 1.000
14 Sidechain Chi_1 dihedral restraints: 120 0 1 65.571 65.571 23.458 1.000
15 Sidechain Chi_2 dihedral restraints: 86 0 0 57.460 57.460 30.234 1.000
16 Sidechain Chi_3 dihedral restraints: 35 0 0 73.876 73.876 23.280 1.000
17 Sidechain Chi_4 dihedral restraints: 20 0 0 99.655 99.655 16.666 1.000
18 Disulfide distance restraints : 4 0 0 0.008 0.008 0.39921E-01 1.000
19 Disulfide angle restraints : 8 0 0 3.078 3.078 1.6733 1.000
20 Disulfide dihedral angle restraints: 4 0 0 23.403 23.403 2.1872 1.000
21 Lower bound distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
22 Upper bound distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
23 Distance restraints 3 (SDCH-MNCH) : 1691 0 0 0.382 0.382 32.072 1.000
24 Sidechain Chi_5 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
25 Phi/Psi pair of dihedral restraints: 146 15 15 20.399 56.678 23.883 1.000
26 Distance restraints 4 (SDCH-SDCH) : 972 0 0 0.605 0.605 51.593 1.000
27 Distance restraints 5 (X-Y) : 0 0 0 0.000 0.000 0.0000 1.000
28 NMR distance restraints 6 (X-Y) : 0 0 0 0.000 0.000 0.0000 1.000
29 NMR distance restraints 7 (X-Y) : 0 0 0 0.000 0.000 0.0000 1.000
30 Minimal distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
31 Non-bonded restraints : 0 0 0 0.000 0.000 0.0000 1.000
32 Atomic accessibility restraints : 0 0 0 0.000 0.000 0.0000 1.000
33 Atomic density restraints : 0 0 0 0.000 0.000 0.0000 1.000
34 Absolute position restraints : 0 0 0 0.000 0.000 0.0000 1.000
35 Dihedral angle difference restraint: 0 0 0 0.000 0.000 0.0000 1.000
36 GBSA implicit solvent potential : 0 0 0 0.000 0.000 0.0000 1.000
37 EM density fitting potential : 0 0 0 0.000 0.000 0.0000 1.000
38 SAXS restraints : 0 0 0 0.000 0.000 0.0000 1.000
39 Symmetry restraints : 0 0 0 0.000 0.000 0.0000 1.000
# Heavy relative violation of each residue is written to: tr|B2R4C5|B2R4C5_HUMAN.V99990001
# The profile is NOT normalized by the number of restraints.
# The profiles are smoothed over a window of residues: 1
# The sum of all numbers in the file: 14242.2764
List of the violated restraints:
A restraint is violated when the relative difference
from the best value (RVIOL) is larger than CUTOFF.
ICSR ... index of a restraint in the current set.
RESNO ... residue numbers of the first two atoms.
ATM ... IUPAC atom names of the first two atoms.
FEAT ... the value of the feature in the model.
restr ... the mean of the basis restraint with the smallest
difference from the model (local minimum).
viol ... difference from the local minimum.
rviol ... relative difference from the local minimum.
RESTR ... the best value (global minimum).
VIOL ... difference from the best value.
RVIOL ... relative difference from the best value.
-------------------------------------------------------------------------------------------------
Feature 25 : Phi/Psi pair of dihedral restraints
List of the RVIOL violations larger than : 6.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 4005 1M 2K C N 7 9 -103.64 -118.00 17.23 0.83 -62.90 175.38 25.17
1 2K 2K N CA 9 10 148.62 139.10 -40.80
2 4006 2K 3A C N 16 18 -67.75 -68.20 4.24 0.36 -62.50 169.66 28.06
2 3A 3A N CA 18 19 149.52 145.30 -40.90
3 4007 3A 4L C N 21 23 -68.87 -70.70 12.19 0.86 -63.50 170.84 23.42
3 4L 4L N CA 23 24 129.55 141.60 -41.20
4 4010 6V 7L C N 44 46 -130.01 -108.50 40.66 1.92 -63.50 165.72 27.13
4 7L 7L N CA 46 47 167.01 132.50 -41.20
5 4011 7L 8G C N 52 54 -96.26 -80.20 43.78 1.06 82.20 -124.49 18.26
5 8G 8G N CA 54 55 -145.17 174.10 8.50
6 4012 8G 9L C N 56 58 -66.89 -70.70 8.62 0.54 -63.50 175.11 24.12
6 9L 9L N CA 58 59 133.87 141.60 -41.20
7 4014 10V 11L C N 71 73 -77.22 -70.70 39.05 3.21 -63.50 144.95 19.38
7 11L 11L N CA 73 74 103.10 141.60 -41.20
8 4015 11L 12L C N 79 81 -97.30 -108.50 44.46 2.27 -63.50 134.98 17.12
8 12L 12L N CA 81 82 89.47 132.50 -41.20
9 4016 12L 13S C N 87 89 -143.24 -136.60 15.64 0.63 -64.10 178.18 18.58
9 13S 13S N CA 89 90 165.36 151.20 -35.00
10 4018 14V 15T C N 100 102 -136.93 -124.80 35.12 1.18 -63.20 159.51 25.23
10 15T 15T N CA 102 103 176.45 143.50 -42.10
11 4020 16V 17Q C N 114 116 -126.28 -121.10 46.54 2.12 -63.80 147.62 24.97
11 17Q 17Q N CA 116 117 -174.05 139.70 -40.30
12 4021 17Q 18G C N 123 125 85.99 78.70 9.43 0.25 82.20 179.45 8.90
12 18G 18G N CA 125 126 -172.09 -166.10 8.50
13 4022 18G 19K C N 127 129 -112.37 -118.00 12.62 0.51 -62.90 175.72 20.66
13 19K 19K N CA 129 130 127.81 139.10 -40.80
14 4057 53E 54S C N 415 417 -139.06 -64.10 82.37 8.75 -64.10 82.37 8.75
14 54S 54S N CA 417 418 -0.84 -35.00 -35.00
15 4069 65A 66G C N 508 510 -66.34 -62.40 6.16 1.12 82.20 158.20 12.08
15 66G 66G N CA 510 511 -45.94 -41.20 8.50
report______> Distribution of short non-bonded contacts:
DISTANCE1: 0.00 2.10 2.20 2.30 2.40 2.50 2.60 2.70 2.80 2.90 3.00 3.10 3.20 3.30 3.40
DISTANCE2: 2.10 2.20 2.30 2.40 2.50 2.60 2.70 2.80 2.90 3.00 3.10 3.20 3.30 3.40 3.50
FREQUENCY: 0 0 0 0 0 2 4 31 62 117 96 135 173 167 201
<< end of ENERGY.
iupac_m_397W> Atoms were not swapped because of the uncertainty of how to handle the H atom.
>> ENERGY; Differences between the model's features and restraints:
Number of all residues in MODEL : 148
Number of all, selected real atoms : 1157 1157
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 12190 12190
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 2411
Dynamic pairs routine : 2, NATM x NATM cell sorting
Atomic shift for contacts update (UPDATE_DYNAMIC) : 0.390
LENNARD_JONES_SWITCH : 6.500 7.500
COULOMB_JONES_SWITCH : 6.500 7.500
RESIDUE_SPAN_RANGE : 0 99999
NLOGN_USE : 15
CONTACT_SHELL : 4.000
DYNAMIC_PAIRS,_SPHERE,_COULOMB,_LENNARD,_MODELLER : T T F F F
SPHERE_STDV : 0.050
RADII_FACTOR : 0.820
Current energy : 742.3640
Summary of the restraint violations:
NUM ... number of restraints.
NUMVI ... number of restraints with RVIOL > VIOL_REPORT_CUT[i].
RVIOL ... relative difference from the best value.
NUMVP ... number of restraints with -Ln(pdf) > VIOL_REPORT_CUT2[i].
RMS_1 ... RMS(feature, minimally_violated_basis_restraint, NUMB).
RMS_2 ... RMS(feature, best_value, NUMB).
MOL.PDF ... scaled contribution to -Ln(Molecular pdf).
# RESTRAINT_GROUP NUM NUMVI NUMVP RMS_1 RMS_2 MOL.PDF S_i
------------------------------------------------------------------------------------------------------
1 Bond length potential : 1177 0 0 0.006 0.006 10.282 1.000
2 Bond angle potential : 1592 0 6 2.029 2.029 133.80 1.000
3 Stereochemical cosine torsion poten: 738 0 25 47.656 47.656 267.93 1.000
4 Stereochemical improper torsion pot: 481 0 0 1.341 1.341 19.336 1.000
5 Soft-sphere overlap restraints : 2411 0 0 0.001 0.001 0.36823 1.000
6 Lennard-Jones 6-12 potential : 0 0 0 0.000 0.000 0.0000 1.000
7 Coulomb point-point electrostatic p: 0 0 0 0.000 0.000 0.0000 1.000
8 H-bonding potential : 0 0 0 0.000 0.000 0.0000 1.000
9 Distance restraints 1 (CA-CA) : 2405 0 0 0.117 0.117 31.519 1.000
10 Distance restraints 2 (N-O) : 2564 0 0 0.147 0.147 62.931 1.000
11 Mainchain Phi dihedral restraints : 0 0 0 0.000 0.000 0.0000 1.000
12 Mainchain Psi dihedral restraints : 0 0 0 0.000 0.000 0.0000 1.000
13 Mainchain Omega dihedral restraints: 147 0 2 4.286 4.286 31.839 1.000
14 Sidechain Chi_1 dihedral restraints: 120 0 2 63.503 63.503 19.095 1.000
15 Sidechain Chi_2 dihedral restraints: 86 0 0 59.230 59.230 29.127 1.000
16 Sidechain Chi_3 dihedral restraints: 35 0 0 76.183 76.183 22.230 1.000
17 Sidechain Chi_4 dihedral restraints: 20 0 0 103.696 103.696 15.298 1.000
18 Disulfide distance restraints : 4 0 0 0.010 0.010 0.74938E-01 1.000
19 Disulfide angle restraints : 8 0 0 2.127 2.127 0.79892 1.000
20 Disulfide dihedral angle restraints: 4 0 0 26.422 26.422 2.8147 1.000
21 Lower bound distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
22 Upper bound distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
23 Distance restraints 3 (SDCH-MNCH) : 1691 0 0 0.403 0.403 32.118 1.000
24 Sidechain Chi_5 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
25 Phi/Psi pair of dihedral restraints: 146 14 14 19.548 54.435 16.560 1.000
26 Distance restraints 4 (SDCH-SDCH) : 972 0 0 0.584 0.584 46.236 1.000
27 Distance restraints 5 (X-Y) : 0 0 0 0.000 0.000 0.0000 1.000
28 NMR distance restraints 6 (X-Y) : 0 0 0 0.000 0.000 0.0000 1.000
29 NMR distance restraints 7 (X-Y) : 0 0 0 0.000 0.000 0.0000 1.000
30 Minimal distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
31 Non-bonded restraints : 0 0 0 0.000 0.000 0.0000 1.000
32 Atomic accessibility restraints : 0 0 0 0.000 0.000 0.0000 1.000
33 Atomic density restraints : 0 0 0 0.000 0.000 0.0000 1.000
34 Absolute position restraints : 0 0 0 0.000 0.000 0.0000 1.000
35 Dihedral angle difference restraint: 0 0 0 0.000 0.000 0.0000 1.000
36 GBSA implicit solvent potential : 0 0 0 0.000 0.000 0.0000 1.000
37 EM density fitting potential : 0 0 0 0.000 0.000 0.0000 1.000
38 SAXS restraints : 0 0 0 0.000 0.000 0.0000 1.000
39 Symmetry restraints : 0 0 0 0.000 0.000 0.0000 1.000
# Heavy relative violation of each residue is written to: tr|B2R4C5|B2R4C5_HUMAN.V99990002
# The profile is NOT normalized by the number of restraints.
# The profiles are smoothed over a window of residues: 1
# The sum of all numbers in the file: 13769.2471
List of the violated restraints:
A restraint is violated when the relative difference
from the best value (RVIOL) is larger than CUTOFF.
ICSR ... index of a restraint in the current set.
RESNO ... residue numbers of the first two atoms.
ATM ... IUPAC atom names of the first two atoms.
FEAT ... the value of the feature in the model.
restr ... the mean of the basis restraint with the smallest
difference from the model (local minimum).
viol ... difference from the local minimum.
rviol ... relative difference from the local minimum.
RESTR ... the best value (global minimum).
VIOL ... difference from the best value.
RVIOL ... relative difference from the best value.
-------------------------------------------------------------------------------------------------
Feature 25 : Phi/Psi pair of dihedral restraints
List of the RVIOL violations larger than : 6.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 4005 1M 2K C N 7 9 -63.54 -70.20 12.73 0.78 -62.90 170.35 22.09
1 2K 2K N CA 9 10 129.55 140.40 -40.80
2 4006 2K 3A C N 16 18 -144.91 -134.00 12.02 0.27 -62.50 -173.72 34.94
2 3A 3A N CA 18 19 152.04 147.00 -40.90
3 4007 3A 4L C N 21 23 -114.90 -108.50 12.24 0.58 -63.50 -176.77 28.61
3 4L 4L N CA 23 24 142.93 132.50 -41.20
4 4010 6V 7L C N 44 46 -67.27 -70.70 17.50 1.20 -63.50 165.68 22.79
4 7L 7L N CA 46 47 124.44 141.60 -41.20
5 4011 7L 8G C N 52 54 85.29 78.70 51.99 1.21 82.20 133.86 6.65
5 8G 8G N CA 54 55 142.33 -166.10 8.50
6 4012 8G 9L C N 56 58 -102.65 -108.50 5.89 0.29 -63.50 178.68 22.87
6 9L 9L N CA 58 59 133.14 132.50 -41.20
7 4014 10V 11L C N 71 73 -115.39 -108.50 20.11 1.00 -63.50 175.26 27.54
7 11L 11L N CA 73 74 151.40 132.50 -41.20
8 4016 12L 13S C N 87 89 -137.19 -136.60 7.53 0.37 -64.10 -178.36 18.37
8 13S 13S N CA 89 90 158.71 151.20 -35.00
9 4018 14V 15T C N 100 102 -145.41 -124.80 37.72 1.17 -63.20 164.78 26.40
9 15T 15T N CA 102 103 175.09 143.50 -42.10
10 4020 16V 17Q C N 114 116 -112.47 -121.10 9.66 0.45 -63.80 -177.72 29.40
10 17Q 17Q N CA 116 117 144.04 139.70 -40.30
11 4021 17Q 18G C N 123 125 60.93 78.70 30.66 0.52 82.20 151.13 8.39
11 18G 18G N CA 125 126 -141.12 -166.10 8.50
12 4022 18G 19K C N 127 129 -114.43 -118.00 26.01 1.21 -62.90 162.53 18.96
12 19K 19K N CA 129 130 113.34 139.10 -40.80
13 4057 53E 54S C N 415 417 -137.30 -64.10 81.48 8.51 -64.10 81.48 8.51
13 54S 54S N CA 417 418 0.79 -35.00 -35.00
14 4069 65A 66G C N 508 510 -67.13 -62.40 5.23 0.99 82.20 158.10 12.03
14 66G 66G N CA 510 511 -43.43 -41.20 8.50
report______> Distribution of short non-bonded contacts:
DISTANCE1: 0.00 2.10 2.20 2.30 2.40 2.50 2.60 2.70 2.80 2.90 3.00 3.10 3.20 3.30 3.40
DISTANCE2: 2.10 2.20 2.30 2.40 2.50 2.60 2.70 2.80 2.90 3.00 3.10 3.20 3.30 3.40 3.50
FREQUENCY: 0 0 0 0 0 5 9 47 70 102 100 130 170 181 194
<< end of ENERGY.
>> Summary of successfully produced models:
Filename molpdf
----------------------------------------
tr|B2R4C5|B2R4C5_HUMAN.B99990001.pdb 784.92761
tr|B2R4C5|B2R4C5_HUMAN.B99990002.pdb 742.36395
In [44]:
# show model
nglview.show_structure_file('tr|B2R4C5|B2R4C5_HUMAN.B99990001.pdb')
In [1]:
Image('without_ligand.png')
Out[1]:
Скачанная последовательность не содержала лиганда, добавим его:
In [29]:
# check ligand positions in pdb structure
alignment[1].residues[0:]
Out[29]:
[Residue 1:A (type LYS), Residue 2:A (type VAL), Residue 3:A (type TYR), Residue 4:A (type ASP), Residue 5:A (type ARG), Residue 6:A (type CYS), Residue 7:A (type GLU), Residue 8:A (type LEU), Residue 9:A (type ALA), Residue 10:A (type ARG), Residue 11:A (type ALA), Residue 12:A (type LEU), Residue 13:A (type LYS), Residue 14:A (type ALA), Residue 15:A (type SER), Residue 16:A (type GLY), Residue 17:A (type MET), Residue 18:A (type ASP), Residue 19:A (type GLY), Residue 20:A (type TYR), Residue 21:A (type ALA), Residue 22:A (type GLY), Residue 23:A (type ASN), Residue 24:A (type SER), Residue 25:A (type LEU), Residue 26:A (type PRO), Residue 27:A (type ASN), Residue 28:A (type TRP), Residue 29:A (type VAL), Residue 30:A (type CYS), Residue 31:A (type LEU), Residue 32:A (type SER), Residue 33:A (type LYS), Residue 34:A (type TRP), Residue 35:A (type GLU), Residue 36:A (type SER), Residue 37:A (type SER), Residue 38:A (type TYR), Residue 39:A (type ASN), Residue 40:A (type THR), Residue 41:A (type GLN), Residue 42:A (type ALA), Residue 43:A (type THR), Residue 44:A (type ASN), Residue 45:A (type ARG), Residue 46:A (type ASN), Residue 47:A (type THR), Residue 48:A (type ASP), Residue 49:A (type GLY), Residue 50:A (type SER), Residue 51:A (type THR), Residue 52:A (type ASP), Residue 53:A (type TYR), Residue 54:A (type GLY), Residue 55:A (type ILE), Residue 56:A (type PHE), Residue 57:A (type GLN), Residue 58:A (type ILE), Residue 59:A (type ASN), Residue 60:A (type SER), Residue 61:A (type ARG), Residue 62:A (type TYR), Residue 63:A (type TRP), Residue 64:A (type CYS), Residue 65:A (type ASP), Residue 66:A (type ASP), Residue 67:A (type GLY), Residue 68:A (type ARG), Residue 69:A (type THR), Residue 70:A (type PRO), Residue 71:A (type GLY), Residue 72:A (type ALA), Residue 73:A (type LYS), Residue 74:A (type ASN), Residue 75:A (type VAL), Residue 76:A (type CYS), Residue 77:A (type GLY), Residue 78:A (type ILE), Residue 79:A (type ARG), Residue 80:A (type CYS), Residue 81:A (type SER), Residue 82:A (type GLN), Residue 83:A (type LEU), Residue 84:A (type LEU), Residue 85:A (type THR), Residue 86:A (type ASP), Residue 87:A (type ASP), Residue 88:A (type LEU), Residue 89:A (type THR), Residue 90:A (type VAL), Residue 91:A (type ALA), Residue 92:A (type ILE), Residue 93:A (type ARG), Residue 94:A (type CYS), Residue 95:A (type ALA), Residue 96:A (type LYS), Residue 97:A (type ARG), Residue 98:A (type VAL), Residue 99:A (type VAL), Residue 100:A (type LEU), Residue 101:A (type ASP), Residue 102:A (type PRO), Residue 103:A (type ASN), Residue 104:A (type GLY), Residue 105:A (type ILE), Residue 106:A (type GLY), Residue 107:A (type ALA), Residue 108:A (type TRP), Residue 109:A (type VAL), Residue 110:A (type ALA), Residue 111:A (type TRP), Residue 112:A (type ARG), Residue 113:A (type LEU), Residue 114:A (type HIS), Residue 115:A (type CYS), Residue 116:A (type GLN), Residue 117:A (type ASN), Residue 118:A (type GLN), Residue 119:A (type ASP), Residue 120:A (type LEU), Residue 121:A (type ARG), Residue 122:A (type SER), Residue 123:A (type TYR), Residue 124:A (type VAL), Residue 125:A (type ALA), Residue 126:A (type GLY), Residue 127:A (type CYS), Residue 128:A (type GLY), Residue 129:A (type VAL), Residue 130:A (type NAG), Residue 131:A (type NAG), Residue 132:A (type NDG)]
In [48]:
# add '.' characters to sequnce for each HETATM records in template
alignment.append_sequence(''.join([x.code for x in alignment[0].residues]+['...']))
In [49]:
# align again
alignment.salign()
alignment.write(file='all_in_one_with_ligand.ali', alignment_format='PIR')
pdb = alignment[1]
s = alignment[2]
# build model with ligand
a = modeller.automodel.automodel(env, alnfile='all_in_one_with_ligand.ali', knowns= pdb.code, sequence = s.code )
a.name='mod'+s.code
a.starting_model = 1
a.ending_model = 1
a.make()
SALIGN_____> adding the next group to the alignment; iteration 1
SALIGN_____> adding the next group to the alignment; iteration 2
SALIGN_____> adding the next group to the alignment; iteration 3
automodel__W> Topology and/or parameter libraries already in memory. These will
be used instead of the automodel defaults. If this is not what you
want, clear them before creating the automodel object with
env.libs.topology.clear() and env.libs.parameters.clear()
fndatmi_285W> Only 129 residues out of 132 contain atoms of type CA
(This is usually caused by non-standard residues, such
as ligands, or by PDB files with missing atoms.)
fndatmi_285W> Only 129 residues out of 132 contain atoms of type CA
(This is usually caused by non-standard residues, such
as ligands, or by PDB files with missing atoms.)
check_ali___> Checking the sequence-structure alignment.
Implied intrachain target CA(i)-CA(i+1) distances longer than 8.0 angstroms:
ALN_POS TMPL RID1 RID2 NAM1 NAM2 DIST
----------------------------------------------
END OF TABLE
getf_______W> RTF restraint not found in the atoms list:
residue type, indices: 18 148
atom names : C +N
atom indices : 1155 0
getf_______W> RTF restraint not found in the atoms list:
residue type, indices: 18 148
atom names : C CA +N O
atom indices : 1155 1151 0 1156
fndatmi_285W> Only 129 residues out of 132 contain atoms of type CA
(This is usually caused by non-standard residues, such
as ligands, or by PDB files with missing atoms.)
patch_s_522_> Number of disulfides patched in MODEL: 4
mdtrsr__446W> A potential that relies on one protein is used, yet you have at
least one known structure available. MDT, not library, potential is used.
iup2crm_280W> No topology library in memory or assigning a BLK residue.
Default CHARMM atom type assigned: C1 --> CT2
This message is written only for the first such atom.
43 atoms in HETATM/BLK residues constrained
to protein atoms within 2.30 angstroms
and protein CA atoms within 10.00 angstroms
43 atoms in residues without defined topology
constrained to be rigid bodies
condens_443_> Restraints marked for deletion were removed.
Total number of restraints before, now: 14595 13591
>> ENERGY; Differences between the model's features and restraints:
Number of all residues in MODEL : 151
Number of all, selected real atoms : 1200 1200
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 13591 13591
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 2521
Dynamic pairs routine : 2, NATM x NATM cell sorting
Atomic shift for contacts update (UPDATE_DYNAMIC) : 0.390
LENNARD_JONES_SWITCH : 6.500 7.500
COULOMB_JONES_SWITCH : 6.500 7.500
RESIDUE_SPAN_RANGE : 0 99999
NLOGN_USE : 15
CONTACT_SHELL : 4.000
DYNAMIC_PAIRS,_SPHERE,_COULOMB,_LENNARD,_MODELLER : T T F F F
SPHERE_STDV : 0.050
RADII_FACTOR : 0.820
Current energy : 1021.3351
Summary of the restraint violations:
NUM ... number of restraints.
NUMVI ... number of restraints with RVIOL > VIOL_REPORT_CUT[i].
RVIOL ... relative difference from the best value.
NUMVP ... number of restraints with -Ln(pdf) > VIOL_REPORT_CUT2[i].
RMS_1 ... RMS(feature, minimally_violated_basis_restraint, NUMB).
RMS_2 ... RMS(feature, best_value, NUMB).
MOL.PDF ... scaled contribution to -Ln(Molecular pdf).
# RESTRAINT_GROUP NUM NUMVI NUMVP RMS_1 RMS_2 MOL.PDF S_i
------------------------------------------------------------------------------------------------------
1 Bond length potential : 1177 0 0 0.006 0.006 13.791 1.000
2 Bond angle potential : 1592 0 8 2.210 2.210 157.87 1.000
3 Stereochemical cosine torsion poten: 738 0 23 46.565 46.565 256.65 1.000
4 Stereochemical improper torsion pot: 481 0 1 1.555 1.555 25.185 1.000
5 Soft-sphere overlap restraints : 2521 1 2 0.008 0.008 17.126 1.000
6 Lennard-Jones 6-12 potential : 0 0 0 0.000 0.000 0.0000 1.000
7 Coulomb point-point electrostatic p: 0 0 0 0.000 0.000 0.0000 1.000
8 H-bonding potential : 0 0 0 0.000 0.000 0.0000 1.000
9 Distance restraints 1 (CA-CA) : 2405 0 0 0.128 0.128 39.681 1.000
10 Distance restraints 2 (N-O) : 2564 2 9 0.228 0.228 134.19 1.000
11 Mainchain Phi dihedral restraints : 0 0 0 0.000 0.000 0.0000 1.000
12 Mainchain Psi dihedral restraints : 0 0 0 0.000 0.000 0.0000 1.000
13 Mainchain Omega dihedral restraints: 147 0 5 4.853 4.853 40.832 1.000
14 Sidechain Chi_1 dihedral restraints: 120 0 2 68.643 68.643 31.763 1.000
15 Sidechain Chi_2 dihedral restraints: 86 0 0 76.233 76.233 45.443 1.000
16 Sidechain Chi_3 dihedral restraints: 35 0 0 81.209 81.209 23.591 1.000
17 Sidechain Chi_4 dihedral restraints: 20 0 1 95.315 95.315 15.611 1.000
18 Disulfide distance restraints : 4 0 0 0.015 0.015 0.16106 1.000
19 Disulfide angle restraints : 8 0 0 2.000 2.000 0.70661 1.000
20 Disulfide dihedral angle restraints: 4 0 0 22.748 22.748 2.0787 1.000
21 Lower bound distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
22 Upper bound distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
23 Distance restraints 3 (SDCH-MNCH) : 1691 0 0 0.465 0.465 51.411 1.000
24 Sidechain Chi_5 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
25 Phi/Psi pair of dihedral restraints: 146 20 21 22.002 62.518 62.808 1.000
26 Distance restraints 4 (SDCH-SDCH) : 972 0 0 0.776 0.776 89.817 1.000
27 Distance restraints 5 (X-Y) : 1401 0 0 0.030 0.030 12.620 1.000
28 NMR distance restraints 6 (X-Y) : 0 0 0 0.000 0.000 0.0000 1.000
29 NMR distance restraints 7 (X-Y) : 0 0 0 0.000 0.000 0.0000 1.000
30 Minimal distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
31 Non-bonded restraints : 0 0 0 0.000 0.000 0.0000 1.000
32 Atomic accessibility restraints : 0 0 0 0.000 0.000 0.0000 1.000
33 Atomic density restraints : 0 0 0 0.000 0.000 0.0000 1.000
34 Absolute position restraints : 0 0 0 0.000 0.000 0.0000 1.000
35 Dihedral angle difference restraint: 0 0 0 0.000 0.000 0.0000 1.000
36 GBSA implicit solvent potential : 0 0 0 0.000 0.000 0.0000 1.000
37 EM density fitting potential : 0 0 0 0.000 0.000 0.0000 1.000
38 SAXS restraints : 0 0 0 0.000 0.000 0.0000 1.000
39 Symmetry restraints : 0 0 0 0.000 0.000 0.0000 1.000
# Heavy relative violation of each residue is written to: alignment_with_ligand.V99990001
# The profile is NOT normalized by the number of restraints.
# The profiles are smoothed over a window of residues: 1
# The sum of all numbers in the file: 16173.0352
List of the violated restraints:
A restraint is violated when the relative difference
from the best value (RVIOL) is larger than CUTOFF.
ICSR ... index of a restraint in the current set.
RESNO ... residue numbers of the first two atoms.
ATM ... IUPAC atom names of the first two atoms.
FEAT ... the value of the feature in the model.
restr ... the mean of the basis restraint with the smallest
difference from the model (local minimum).
viol ... difference from the local minimum.
rviol ... relative difference from the local minimum.
RESTR ... the best value (global minimum).
VIOL ... difference from the best value.
RVIOL ... relative difference from the best value.
-------------------------------------------------------------------------------------------------
Feature 10 : Distance restraints 2 (N-O)
List of the RVIOL violations larger than : 4.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 7937 65A 89P N O 505 705 14.13 10.99 3.14 4.52 10.99 3.14 4.52
2 7973 69S 89P N O 533 705 8.64 6.49 2.15 4.73 6.49 2.15 4.73
-------------------------------------------------------------------------------------------------
Feature 25 : Phi/Psi pair of dihedral restraints
List of the RVIOL violations larger than : 6.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 4005 1M 2K C N 7 9 -80.08 -70.20 23.88 1.51 -62.90 157.99 21.50
1 2K 2K N CA 9 10 162.14 140.40 -40.80
2 4006 2K 3A C N 16 18 -70.50 -68.20 20.12 1.54 -62.50 154.02 25.64
2 3A 3A N CA 18 19 165.29 145.30 -40.90
3 4007 3A 4L C N 21 23 -67.30 -70.70 13.26 1.14 -63.50 164.42 23.05
3 4L 4L N CA 23 24 154.42 141.60 -41.20
4 4010 6V 7L C N 44 46 -60.09 -70.70 20.76 1.96 -63.50 159.39 21.94
4 7L 7L N CA 46 47 159.45 141.60 -41.20
5 4011 7L 8G C N 52 54 113.73 78.70 56.54 1.04 82.20 144.50 8.55
5 8G 8G N CA 54 55 149.52 -166.10 8.50
6 4012 8G 9L C N 56 58 -67.69 -70.70 3.39 0.25 -63.50 178.81 25.07
6 9L 9L N CA 58 59 140.04 141.60 -41.20
7 4014 10V 11L C N 71 73 -109.62 -108.50 3.17 0.16 -63.50 -177.41 23.14
7 11L 11L N CA 73 74 135.47 132.50 -41.20
8 4015 11L 12L C N 79 81 -110.34 -108.50 3.57 0.20 -63.50 176.96 22.36
8 12L 12L N CA 81 82 129.45 132.50 -41.20
9 4016 12L 13S C N 87 89 -155.31 -136.60 43.18 1.72 -64.10 162.82 18.38
9 13S 13S N CA 89 90 -169.88 151.20 -35.00
10 4017 13S 14V C N 93 95 -60.47 -62.40 9.49 1.10 -125.40 177.33 10.00
10 14V 14V N CA 95 96 -51.69 -42.40 143.30
11 4018 14V 15T C N 100 102 -95.14 -78.10 39.64 1.30 -63.20 136.11 19.59
11 15T 15T N CA 102 103 -174.41 149.80 -42.10
12 4020 16V 17Q C N 114 116 -125.37 -121.10 19.98 0.87 -63.80 171.88 28.53
12 17Q 17Q N CA 116 117 159.22 139.70 -40.30
13 4021 17Q 18G C N 123 125 -161.22 -167.20 7.22 0.24 82.20 -153.75 15.06
13 18G 18G N CA 125 126 178.64 174.60 8.50
14 4022 18G 19K C N 127 129 -71.45 -70.20 21.71 1.60 -62.90 159.75 20.29
14 19K 19K N CA 129 130 118.72 140.40 -40.80
15 4057 53E 54S C N 415 417 -133.61 -64.10 74.83 8.18 -64.10 74.83 8.18
15 54S 54S N CA 417 418 -7.28 -35.00 -35.00
16 4069 65A 66G C N 508 510 -139.94 -62.40 86.54 13.48 82.20 138.32 8.85
16 66G 66G N CA 510 511 -2.77 -41.20 8.50
17 4092 88T 89P C N 697 699 -51.77 -58.70 51.99 3.76 -64.50 131.39 10.49
17 89P 89P N CA 699 700 -82.03 -30.50 147.20
18 4093 89P 90G C N 704 706 -65.75 -62.40 28.08 4.04 82.20 149.55 10.75
18 90G 90G N CA 706 707 -13.32 -41.20 8.50
19 4138 134C 135Q C N 1043 1045 -57.34 -63.80 14.52 1.88 -73.00 166.72 11.22
19 135Q 135Q N CA 1045 1046 -53.31 -40.30 140.70
20 4139 135Q 136N C N 1052 1054 -116.14 -119.90 70.17 3.10 55.90 174.22 18.12
20 136N 136N N CA 1054 1055 66.94 137.00 39.50
report______> Distribution of short non-bonded contacts:
DISTANCE1: 0.00 2.10 2.20 2.30 2.40 2.50 2.60 2.70 2.80 2.90 3.00 3.10 3.20 3.30 3.40
DISTANCE2: 2.10 2.20 2.30 2.40 2.50 2.60 2.70 2.80 2.90 3.00 3.10 3.20 3.30 3.40 3.50
FREQUENCY: 0 0 0 0 1 8 8 52 83 140 111 142 177 187 209
<< end of ENERGY.
>> Summary of successfully produced models:
Filename molpdf
----------------------------------------
alignment_with_ligand.B99990001.pdb 1021.33508
In [50]:
# show model structure with ligand
nglview.show_structure_file('alignment_with_ligand.B99990001.pdb')
In [2]:
Image('with_ligand.png')
Out[2]:
In [4]:
%%bash
jupyter nbconvert --to html hw6_filippova.ipynb
[NbConvertApp] Converting notebook hw6_filippova.ipynb to html [NbConvertApp] Writing 473759 bytes to hw6_filippova.html