In [72]:
#загрузим модуль
import pandas as pd
import numpy as np
import sys
import modeller
import _modeller
import modeller.automodel
import nglview
import ipywidgets
from IPython.display import Image
#зададим параметры
env = modeller.environ()
env.io.hetatm = True
Выбрала белок лизоцим С с id P85045 из Bufo gargarizans andrewsi¶
In [4]:
Image("https://i.pinimg.com/564x/a7/d1/44/a7d144e39115901d2fd11c283f1a0e86.jpg")
Out[4]:
In [3]:
# скачаем белок заготовку
! wget http://www.pdb.org/pdb/files/1lmp.pdb
# скачаем последовательность
! wget https://www.uniprot.org/uniprot/P85045.fasta
--2021-05-27 03:43:33-- http://www.pdb.org/pdb/files/1lmp.pdb
Resolving www.pdb.org (www.pdb.org)... 128.6.159.96
Connecting to www.pdb.org (www.pdb.org)|128.6.159.96|:80... connected.
HTTP request sent, awaiting response... 301 Moved Permanently
Location: https://www.rcsb.org/pdb/files/1lmp.pdb [following]
--2021-05-27 03:43:33-- https://www.rcsb.org/pdb/files/1lmp.pdb
Resolving www.rcsb.org (www.rcsb.org)... 128.6.159.248
Connecting to www.rcsb.org (www.rcsb.org)|128.6.159.248|:443... connected.
HTTP request sent, awaiting response... 301 Moved Permanently
Location: https://files.rcsb.org/download/1lmp.pdb [following]
--2021-05-27 03:43:34-- https://files.rcsb.org/download/1lmp.pdb
Resolving files.rcsb.org (files.rcsb.org)... 128.6.158.49
Connecting to files.rcsb.org (files.rcsb.org)|128.6.158.49|:443... connected.
HTTP request sent, awaiting response... 200 OK
Length: unspecified [application/octet-stream]
Saving to: `1lmp.pdb.4'
[ <=> ] 128,871 342K/s in 0.4s
2021-05-27 03:43:36 (342 KB/s) - `1lmp.pdb.4' saved [128871]
--2021-05-27 03:43:36-- https://www.uniprot.org/uniprot/P85045.fasta
Resolving www.uniprot.org (www.uniprot.org)... 128.175.240.206, 193.62.193.81
Connecting to www.uniprot.org (www.uniprot.org)|128.175.240.206|:443... connected.
HTTP request sent, awaiting response... 200
Length: 240 [text/plain]
Saving to: `P85045.fasta.3'
100%[======================================>] 240 --.-K/s in 0s
2021-05-27 03:43:37 (113 MB/s) - `P85045.fasta.3' saved [240/240]
Выровняем последовательности лизоцима форели и лизоцима жабы¶
In [2]:
# создадим объект выравнивание
alignm=modeller.alignment(env)
alignm.append(file='P85045.fasta',
align_codes='all',
alignment_format='FASTA')
# создадим модель
mdl = modeller.model(env,
file='1lmp.pdb',
model_segment=('FIRST:'+'A', 'LAST:'+'B'))
# и добавим в выравнивание
alignm.append_model(mdl,
atom_files='1lmp.pdb',
align_codes='1lmp')
# есть смысл поправить идентификаторы
alignm[0].code = 'seq'
alignm[1].code = 'pdb'
read_pd_459W> Residue type NDG not recognized. 'automodel' model building
will treat this residue as a rigid body.
To use real parameters, add the residue type to ${LIB}/restyp.lib,
its topology to ${LIB}/top_*.lib, and suitable forcefield
parameters to ${LIB}/par.lib.
read_pd_459W> Residue type NAG not recognized. 'automodel' model building
will treat this residue as a rigid body.
To use real parameters, add the residue type to ${LIB}/restyp.lib,
its topology to ${LIB}/top_*.lib, and suitable forcefield
parameters to ${LIB}/par.lib.
In [3]:
# делаем выравнивание.
alignm.salign()
# сохраняем в файл.
alignm.write(file='all_in_one.ali', alignment_format='PIR')
SALIGN_____> adding the next group to the alignment; iteration 1
Проверим, все ли хорошо в выравнивании
In [4]:
!cat all_in_one.ali
>P1;seq sequence:: : : : :::-1.00:-1.00 SGKYISWEDSCSYLQLQKYERCELAKALKKGGLADFKGYSLENWICTAFHESGYNTASTNYNPPDKSTDYGIFQI NSRWWCNDYKTPRSKNTCNIDCKVLLGDDISPAIKCAKRVVSDPNGMGAWVAWKKYCKGKNLSQWTQGCKL----* >P1;pdb structureX:1lmp.pdb: 1 :A:+132 :B: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-DGSTDYGIFQI NSRYWCDDGRTPGAKNVCGIRCSQLLTDDLTVAIRCAKRVVLDPNGIGAWVAWRLHCQNQDLRSYVAGCGV/...*
Вроде бы выравнивание адекватное
Моделируем структуру лизоцима жабы¶
In [5]:
# выбираем объект для моделирования
s = alignm[0]
pdb = alignm[1]
print (s.code, pdb.code)
# создаем объект automodel
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 = 2
a.make()
seq pdb
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: 13044 12008
>> ENERGY; Differences between the model's features and restraints:
Number of all residues in MODEL : 146
Number of all, selected real atoms : 1166 1166
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 12008 12008
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 2439
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 : 780.6552
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 : 1197 0 0 0.006 0.006 11.149 1.000
2 Bond angle potential : 1618 0 5 2.105 2.105 141.55 1.000
3 Stereochemical cosine torsion poten: 814 0 31 47.816 47.816 280.45 1.000
4 Stereochemical improper torsion pot: 502 0 0 1.213 1.213 17.222 1.000
5 Soft-sphere overlap restraints : 2439 0 0 0.002 0.002 0.72972 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 36.267 1.000
10 Distance restraints 2 (N-O) : 2564 0 2 0.189 0.189 79.077 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: 145 0 2 4.123 4.123 29.063 1.000
14 Sidechain Chi_1 dihedral restraints: 126 0 0 62.861 62.861 14.837 1.000
15 Sidechain Chi_2 dihedral restraints: 93 0 0 75.994 75.994 31.311 1.000
16 Sidechain Chi_3 dihedral restraints: 37 0 0 75.895 75.895 24.630 1.000
17 Sidechain Chi_4 dihedral restraints: 21 0 0 76.648 76.648 12.125 1.000
18 Disulfide distance restraints : 4 0 0 0.006 0.006 0.27081E-01 1.000
19 Disulfide angle restraints : 8 0 0 1.713 1.713 0.51828 1.000
20 Disulfide dihedral angle restraints: 4 0 0 32.504 32.504 3.5620 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) : 1582 0 0 0.356 0.356 26.992 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: 144 16 11 22.071 57.753 36.114 1.000
26 Distance restraints 4 (SDCH-SDCH) : 744 0 0 0.564 0.564 35.035 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: seq.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: 14269.6729
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 4149 2G 3K C N 9 11 -120.79 -118.00 23.53 1.10 -62.90 167.08 25.16
1 3K 3K N CA 11 12 162.47 139.10 -40.80
2 4150 3K 4Y C N 18 20 -123.86 -124.30 10.54 0.58 -63.50 -178.98 31.76
2 4Y 4Y N CA 20 21 145.94 135.40 -43.40
3 4152 5I 6S C N 38 40 -59.66 -72.40 27.37 1.27 -64.10 163.24 12.10
3 6S 6S N CA 40 41 128.18 152.40 -35.00
4 4153 6S 7W C N 44 46 -145.63 -124.90 26.75 0.85 -63.00 176.08 27.58
4 7W 7W N CA 46 47 160.31 143.40 -44.20
5 4154 7W 8E C N 58 60 -96.67 -117.80 26.27 0.79 -63.60 164.85 20.34
5 8E 8E N CA 60 61 121.20 136.80 -40.30
6 4155 8E 9D C N 67 69 -99.59 -96.50 10.78 0.45 -63.30 148.38 16.46
6 9D 9D N CA 69 70 103.88 114.20 -40.00
7 4156 9D 10S C N 75 77 -74.92 -72.40 2.69 0.16 -64.10 171.99 13.13
7 10S 10S N CA 77 78 153.35 152.40 -35.00
8 4158 11C 12S C N 87 89 -148.70 -136.60 14.70 0.79 -64.10 -163.06 12.43
8 12S 12S N CA 89 90 142.85 151.20 -35.00
9 4159 12S 13Y C N 93 95 -122.42 -124.30 8.89 0.40 -63.50 -179.97 25.87
9 13Y 13Y N CA 95 96 126.72 135.40 -43.40
10 4160 13Y 14L C N 105 107 -119.46 -108.50 33.50 1.89 -63.50 152.67 18.87
10 14L 14L N CA 107 108 100.85 132.50 -41.20
11 4162 15Q 16L C N 122 124 -53.03 -70.70 19.77 1.46 -63.50 174.25 24.81
11 16L 16L N CA 124 125 132.74 141.60 -41.20
12 4163 16L 17Q C N 130 132 -105.26 -121.10 23.59 0.78 -63.80 167.72 22.70
12 17Q 17Q N CA 132 133 122.22 139.70 -40.30
13 4198 51E 52S C N 414 416 -137.65 -64.10 81.25 8.57 -64.10 81.25 8.57
13 52S 52S N CA 416 417 -0.47 -35.00 -35.00
14 4210 63P 64P C N 504 506 -70.41 -58.70 12.43 1.74 -64.50 178.24 12.99
14 64P 64P N CA 506 507 -34.66 -30.50 147.20
15 4288 141T 142Q C N 1128 1130 22.63 -63.80 126.37 16.40 -73.00 129.16 10.05
15 142Q 142Q N CA 1130 1131 -132.49 -40.30 140.70
16 4289 142Q 143G C N 1137 1139 -59.05 -62.40 25.69 4.01 82.20 143.32 10.39
16 143G 143G N CA 1139 1140 -15.73 -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 9 10 52 80 107 102 124 149 205 193
<< end of ENERGY.
>> ENERGY; Differences between the model's features and restraints:
Number of all residues in MODEL : 146
Number of all, selected real atoms : 1166 1166
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 12008 12008
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 2404
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 : 801.2952
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 : 1197 0 0 0.006 0.006 11.978 1.000
2 Bond angle potential : 1618 0 5 2.162 2.162 149.18 1.000
3 Stereochemical cosine torsion poten: 814 0 32 47.853 47.853 280.75 1.000
4 Stereochemical improper torsion pot: 502 0 0 1.354 1.354 20.247 1.000
5 Soft-sphere overlap restraints : 2404 0 0 0.001 0.001 0.35712 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 0.131 0.131 38.348 1.000
10 Distance restraints 2 (N-O) : 2564 0 0 0.160 0.160 68.636 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: 145 0 2 4.384 4.384 32.860 1.000
14 Sidechain Chi_1 dihedral restraints: 126 0 0 62.575 62.575 18.316 1.000
15 Sidechain Chi_2 dihedral restraints: 93 0 0 69.418 69.418 40.661 1.000
16 Sidechain Chi_3 dihedral restraints: 37 0 0 86.894 86.894 28.468 1.000
17 Sidechain Chi_4 dihedral restraints: 21 0 0 80.626 80.626 15.307 1.000
18 Disulfide distance restraints : 4 0 0 0.008 0.008 0.41274E-01 1.000
19 Disulfide angle restraints : 8 0 0 1.807 1.807 0.57662 1.000
20 Disulfide dihedral angle restraints: 4 0 0 29.943 29.943 3.3804 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) : 1582 0 0 0.396 0.396 25.516 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: 144 15 13 23.637 57.466 34.828 1.000
26 Distance restraints 4 (SDCH-SDCH) : 744 0 0 0.553 0.553 31.843 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: seq.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: 14322.9121
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 4148 1S 2G C N 5 7 84.65 78.70 18.28 0.30 82.20 168.13 8.29
1 2G 2G N CA 7 8 176.61 -166.10 8.50
2 4149 2G 3K C N 9 11 -134.03 -118.00 17.24 0.77 -62.90 -172.44 21.65
2 3K 3K N CA 11 12 132.75 139.10 -40.80
3 4150 3K 4Y C N 18 20 -69.76 -98.40 29.28 1.35 -63.50 165.84 26.00
3 4Y 4Y N CA 20 21 122.32 128.40 -43.40
4 4152 5I 6S C N 38 40 -97.98 -72.40 30.14 2.43 -64.10 174.77 11.11
4 6S 6S N CA 40 41 136.45 152.40 -35.00
5 4153 6S 7W C N 44 46 -137.58 -124.90 26.77 0.97 -63.00 166.47 25.83
5 7W 7W N CA 46 47 166.98 143.40 -44.20
6 4154 7W 8E C N 58 60 -124.25 -117.80 27.79 1.49 -63.60 161.86 19.00
6 8E 8E N CA 60 61 109.76 136.80 -40.30
7 4155 8E 9D C N 67 69 -104.74 -70.90 50.74 1.94 -63.30 138.26 19.74
7 9D 9D N CA 69 70 -171.90 150.30 -40.00
8 4156 9D 10S C N 75 77 -82.52 -72.40 15.03 0.70 -64.10 162.53 12.96
8 10S 10S N CA 77 78 163.51 152.40 -35.00
9 4158 11C 12S C N 87 89 -93.14 -72.40 80.23 5.43 -64.10 113.67 7.06
9 12S 12S N CA 89 90 74.90 152.40 -35.00
10 4159 12S 13Y C N 93 95 -125.64 -124.30 17.63 0.99 -63.50 172.78 24.63
10 13Y 13Y N CA 95 96 117.82 135.40 -43.40
11 4160 13Y 14L C N 105 107 -96.37 -108.50 24.86 1.42 -63.50 167.84 25.30
11 14L 14L N CA 107 108 154.21 132.50 -41.20
12 4162 15Q 16L C N 122 124 -69.37 -70.70 16.30 1.29 -63.50 161.05 22.70
12 16L 16L N CA 124 125 157.85 141.60 -41.20
13 4163 16L 17Q C N 130 132 -76.68 -73.00 6.86 0.52 -63.80 175.69 25.17
13 17Q 17Q N CA 132 133 134.92 140.70 -40.30
14 4198 51E 52S C N 414 416 -136.57 -64.10 80.80 8.42 -64.10 80.80 8.42
14 52S 52S N CA 416 417 0.72 -35.00 -35.00
15 4210 63P 64P C N 504 506 -70.52 -58.70 12.13 1.67 -64.50 179.68 13.09
15 64P 64P N CA 506 507 -33.22 -30.50 147.20
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 3 5 37 63 119 119 150 168 186 179
<< end of ENERGY.
>> Summary of successfully produced models:
Filename molpdf
----------------------------------------
seq.B99990001.pdb 780.65515
seq.B99990002.pdb 801.29517
Посмотрим что получилось¶
Кажется создалось 2 модели B99990001 и B99990002, посмотрим как выглядят обе и сравним с референсом
In [43]:
#Используем команду для выравнивания стуктур в pymol чтобы сравнивать их
def show_model(pdb_1, pdb_2, name):
command = f"load {pdb_1}, model_1; load {pdb_2}, model_2; " \
f"util.cbas model_1; util.cbab model_2; " \
f"align model_1, model_2; " \
f"as cartoon; as sticks, hetatm; " \
f"as cartoon; as sticks, hetatm; orient; " \
f"set ray_trace_mode, 3; set antialias, 2; bg_color white;set transparency, 0.5; " \
f"png {name}.png"
! pymol -Qcd "$command"
display(Image(f'{name}.png'))
In [38]:
# посмотрим на первую структуру
model1 = nglview.show_structure_file('seq.B99990001.pdb')
model1.clear_representations()
model1.add_cartoon('protein', color_scheme='residueindex')
model1.add_ball_and_stick('ligand', opacity=0.5)
model1
In [44]:
# сравним жабу с форелью синим будет форель, а красным - жаба
show_model("seq.B99990001.pdb","1lmp.pdb",1 )
In [14]:
# посмотрим на вторую струткуру
model2 = nglview.show_structure_file('seq.B99990002.pdb')
model2.clear_representations()
model2.add_cartoon('protein', color_scheme='residueindex')
model2.add_ball_and_stick('ligand', opacity=0.5)
model2
In [45]:
# сравним жабу с форелью синим будет форель, а красным - жаба
show_model("seq.B99990002.pdb","1lmp.pdb",2 )
Видим что в среднем смоделированные структуры довольно похожи на оригинальную структуру, но плохо смоделировался N конец, что логично, потому что белок жабы плохо выравнивается с белком форели с N конца. У форели на N конце спираль, а у жабы получилась неструктурированная петля.
Добавим лиганд в последовательность белка жабы¶
In [16]:
seq_liganded = ''
for res in alignm[0].residues:
seq_liganded += res.code
for lig in alignm[1].residues[-3:]:
seq_liganded += lig.code
alignm.append_sequence(seq_liganded)
alignm[2].code = 'seq_liganded'
del alignm[0]
In [17]:
# делаем выравнивание.
alignm.salign()
# сохраняем в файл.
alignm.write(file='all_in_one2.ali', alignment_format='PIR')
SALIGN_____> adding the next group to the alignment; iteration 1
In [18]:
!cat all_in_one2.ali
>P1;pdb structureX:1lmp.pdb: 1 :A:+132 :B: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-DGSTDYGIFQI NSRYWCDDGRTPGAKNVCGIRCSQLLTDDLTVAIRCAKRVVLDPNGIGAWVAWRLHCQNQDLRSYVAGCGV/...* >P1;seq_liganded sequence::1 : :+149 : :undefined:undefined:-1.00:-1.00 SGKYISWEDSCSYLQLQKYERCELAKALKKGGLADFKGYSLENWICTAFHESGYNTASTNYNPPDKSTDYGIFQI NSRWWCNDYKTPRSKNTCNIDCKVLLGDDISPAIKCAKRVVSDPNGMGAWVAWKKYCKGKNLSQWTQGCKL-...*
О, теперь видим что в последовательность белка жабы добавились точки в конец, видимо это и есть лиганд, ведь мы дописывали его в конец последовательности.
Смоделируем структуру лизоцима жабы с учетом лиганда¶
In [19]:
# Выбираем объект для моделирования.
s = alignm[1]
pdb = alignm[0]
print(s.code, pdb.code)
# Создаем объект automodel.
a = modeller.automodel.automodel(env, alnfile='all_in_one2.ali', knowns=pdb.code, sequence=s.code)
a.name = 'mod' + s.code
a.starting_model = 1
a.ending_model = 2
a.make()
seq_liganded pdb
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: 10 146
atom names : C +N
atom indices : 1164 0
getf_______W> RTF restraint not found in the atoms list:
residue type, indices: 10 146
atom names : C CA +N O
atom indices : 1164 1159 0 1165
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: 14445 13409
iupac_m_397W> Atoms were not swapped because of the uncertainty of how to handle the H atom.
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 : 149
Number of all, selected real atoms : 1209 1209
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 13409 13409
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 2546
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 : 921.4798
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 : 1197 0 0 0.006 0.006 12.685 1.000
2 Bond angle potential : 1618 0 8 2.221 2.221 158.14 1.000
3 Stereochemical cosine torsion poten: 814 0 28 46.951 46.951 277.97 1.000
4 Stereochemical improper torsion pot: 502 0 0 1.314 1.314 19.376 1.000
5 Soft-sphere overlap restraints : 2546 2 2 0.008 0.008 17.920 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 0.119 0.119 35.450 1.000
10 Distance restraints 2 (N-O) : 2564 0 3 0.191 0.191 86.668 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: 145 0 3 4.609 4.609 36.326 1.000
14 Sidechain Chi_1 dihedral restraints: 126 0 1 70.001 70.001 24.151 1.000
15 Sidechain Chi_2 dihedral restraints: 93 0 0 70.005 70.005 28.187 1.000
16 Sidechain Chi_3 dihedral restraints: 37 0 0 77.266 77.266 23.337 1.000
17 Sidechain Chi_4 dihedral restraints: 21 0 0 67.070 67.070 12.483 1.000
18 Disulfide distance restraints : 4 0 0 0.009 0.009 0.56218E-01 1.000
19 Disulfide angle restraints : 8 0 0 1.651 1.651 0.48168 1.000
20 Disulfide dihedral angle restraints: 4 0 0 32.692 32.692 3.7501 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) : 1582 0 0 0.493 0.493 56.540 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: 144 18 13 20.810 62.699 38.965 1.000
26 Distance restraints 4 (SDCH-SDCH) : 744 0 0 0.814 0.814 76.871 1.000
27 Distance restraints 5 (X-Y) : 1401 0 0 0.030 0.030 12.130 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: seq_liganded.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: 15635.0195
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 4148 1S 2G C N 5 7 -119.63 -80.20 49.21 3.59 82.20 -151.30 16.18
1 2G 2G N CA 7 8 144.65 174.10 8.50
2 4149 2G 3K C N 9 11 -134.17 -118.00 38.64 1.60 -62.90 161.57 25.25
2 3K 3K N CA 11 12 174.20 139.10 -40.80
3 4150 3K 4Y C N 18 20 -131.16 -124.30 17.49 0.70 -63.50 178.44 31.69
3 4Y 4Y N CA 20 21 151.48 135.40 -43.40
4 4152 5I 6S C N 38 40 -137.42 -136.60 18.70 0.93 -64.10 171.58 17.67
4 6S 6S N CA 40 41 169.88 151.20 -35.00
5 4153 6S 7W C N 44 46 -98.42 -124.90 27.50 1.39 -63.00 168.73 23.41
5 7W 7W N CA 46 47 150.83 143.40 -44.20
6 4155 8E 9D C N 67 69 -93.71 -96.50 26.42 1.11 -63.30 131.49 14.65
6 9D 9D N CA 69 70 87.93 114.20 -40.00
7 4156 9D 10S C N 75 77 -133.03 -136.60 15.97 0.73 -64.10 -175.97 11.40
7 10S 10S N CA 77 78 135.63 151.20 -35.00
8 4158 11C 12S C N 87 89 -67.49 -72.40 12.66 0.91 -64.10 160.96 11.87
8 12S 12S N CA 89 90 164.07 152.40 -35.00
9 4159 12S 13Y C N 93 95 -129.45 -124.30 32.82 1.53 -63.50 162.74 29.09
9 13Y 13Y N CA 95 96 167.82 135.40 -43.40
10 4160 13Y 14L C N 105 107 -61.14 -70.70 14.19 1.40 -63.50 166.73 23.02
10 14L 14L N CA 107 108 152.09 141.60 -41.20
11 4161 14L 15Q C N 113 115 -59.77 -73.00 31.68 1.85 -63.80 152.28 22.60
11 15Q 15Q N CA 115 116 111.92 140.70 -40.30
12 4162 15Q 16L C N 122 124 -149.73 -108.50 41.37 2.01 -63.50 -169.15 23.39
12 16L 16L N CA 124 125 129.05 132.50 -41.20
13 4163 16L 17Q C N 130 132 -129.23 -121.10 11.13 0.57 -63.80 -175.60 24.25
13 17Q 17Q N CA 132 133 132.10 139.70 -40.30
14 4198 51E 52S C N 414 416 -136.69 -64.10 78.43 8.53 -64.10 78.43 8.53
14 52S 52S N CA 416 417 -5.31 -35.00 -35.00
15 4209 62N 63P C N 497 499 -65.00 -64.50 60.10 4.46 -58.70 122.37 10.63
15 63P 63P N CA 499 500 -152.71 147.20 -30.50
16 4210 63P 64P C N 504 506 -57.26 -58.70 26.30 2.29 -64.50 151.61 10.94
16 64P 64P N CA 506 507 -4.24 -30.50 147.20
17 4279 132C 133K C N 1054 1056 -51.38 -62.90 28.58 3.29 -70.20 153.80 11.58
17 133K 133K N CA 1056 1057 -66.96 -40.80 140.40
18 4280 133K 134G C N 1063 1065 -75.04 -62.40 15.04 2.26 82.20 162.64 12.14
18 134G 134G N CA 1065 1066 -33.05 -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 1 11 10 59 77 133 116 159 161 203 194
<< end of ENERGY.
iupac_m_397W> Atoms were not swapped because of the uncertainty of how to handle the H atom.
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 : 149
Number of all, selected real atoms : 1209 1209
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 13409 13409
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 2512
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 : 1004.9974
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 : 1197 0 0 0.006 0.006 13.745 1.000
2 Bond angle potential : 1618 0 7 2.294 2.294 169.78 1.000
3 Stereochemical cosine torsion poten: 814 0 28 47.224 47.224 280.79 1.000
4 Stereochemical improper torsion pot: 502 0 0 1.354 1.354 21.307 1.000
5 Soft-sphere overlap restraints : 2512 1 2 0.008 0.008 16.917 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 0.139 0.139 46.539 1.000
10 Distance restraints 2 (N-O) : 2564 3 11 0.238 0.238 141.27 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: 145 1 4 5.191 5.191 46.080 1.000
14 Sidechain Chi_1 dihedral restraints: 126 0 0 67.544 67.544 20.366 1.000
15 Sidechain Chi_2 dihedral restraints: 93 0 0 75.245 75.245 31.964 1.000
16 Sidechain Chi_3 dihedral restraints: 37 0 0 78.746 78.746 22.039 1.000
17 Sidechain Chi_4 dihedral restraints: 21 0 0 84.722 84.722 13.055 1.000
18 Disulfide distance restraints : 4 0 0 0.008 0.008 0.46955E-01 1.000
19 Disulfide angle restraints : 8 0 0 1.756 1.756 0.54442 1.000
20 Disulfide dihedral angle restraints: 4 0 0 30.012 30.012 3.4433 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) : 1582 0 0 0.367 0.367 36.439 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: 144 22 19 30.074 71.456 91.836 1.000
26 Distance restraints 4 (SDCH-SDCH) : 744 0 0 0.551 0.551 34.830 1.000
27 Distance restraints 5 (X-Y) : 1401 0 0 0.033 0.033 14.009 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: seq_liganded.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: 16373.9600
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 9264 121G 37K N O 959 298 10.25 7.92 2.32 4.59 7.92 2.32 4.59
2 9279 122M 37K N O 963 298 9.28 6.93 2.35 5.27 6.93 2.35 5.27
3 9299 123G 37K N O 971 298 11.69 9.33 2.36 4.86 9.33 2.36 4.86
-------------------------------------------------------------------------------------------------
Feature 13 : Mainchain Omega dihedral restraints
List of the RVIOL violations larger than : 4.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 4329 38G 38G CA C 300 301 -154.73 -180.00 25.27 5.05 -180.00 25.27 5.05
-------------------------------------------------------------------------------------------------
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 4149 2G 3K C N 9 11 -72.10 -70.20 2.00 0.13 -62.90 178.44 23.69
1 3K 3K N CA 11 12 141.00 140.40 -40.80
2 4150 3K 4Y C N 18 20 -115.48 -124.30 8.84 0.65 -63.50 -174.36 27.01
2 4Y 4Y N CA 20 21 134.81 135.40 -43.40
3 4152 5I 6S C N 38 40 -66.43 -72.40 14.18 0.66 -64.10 174.55 12.51
3 6S 6S N CA 40 41 139.53 152.40 -35.00
4 4153 6S 7W C N 44 46 -131.20 -124.90 17.15 0.67 -63.00 170.66 25.92
4 7W 7W N CA 46 47 159.36 143.40 -44.20
5 4154 7W 8E C N 58 60 -113.75 -117.80 14.35 0.63 -63.60 170.86 20.47
5 8E 8E N CA 60 61 123.03 136.80 -40.30
6 4155 8E 9D C N 67 69 -135.85 -96.50 39.38 1.61 -63.30 169.03 17.96
6 9D 9D N CA 69 70 112.67 114.20 -40.00
7 4156 9D 10S C N 75 77 -138.39 -136.60 3.94 0.15 -64.10 -174.21 18.75
7 10S 10S N CA 77 78 154.71 151.20 -35.00
8 4158 11C 12S C N 87 89 -71.43 -72.40 32.51 1.95 -64.10 140.30 10.62
8 12S 12S N CA 89 90 -175.11 152.40 -35.00
9 4159 12S 13Y C N 93 95 -52.68 -98.40 46.45 1.87 -63.50 -179.71 29.16
9 13Y 13Y N CA 95 96 136.56 128.40 -43.40
10 4160 13Y 14L C N 105 107 -83.91 -70.70 18.82 1.20 -63.50 165.07 24.14
10 14L 14L N CA 107 108 155.00 141.60 -41.20
11 4161 14L 15Q C N 113 115 93.73 -121.10 145.32 5.33 -63.80 -125.62 30.34
11 15Q 15Q N CA 115 116 146.15 139.70 -40.30
12 4162 15Q 16L C N 122 124 -83.74 -70.70 19.60 1.23 -63.50 163.82 23.96
12 16L 16L N CA 124 125 156.24 141.60 -41.20
13 4163 16L 17Q C N 130 132 -112.51 -121.10 21.46 0.85 -63.80 167.57 22.40
13 17Q 17Q N CA 132 133 120.03 139.70 -40.30
14 4183 36F 37K C N 288 290 67.06 -62.90 159.83 20.70 56.60 172.75 11.57
14 37K 37K N CA 290 291 -133.84 -40.80 38.60
15 4184 37K 38G C N 297 299 -91.49 -62.40 38.06 5.49 82.20 175.51 12.60
15 38G 38G N CA 299 300 -16.66 -41.20 8.50
16 4198 51E 52S C N 414 416 -137.38 -64.10 81.51 8.52 -64.10 81.51 8.52
16 52S 52S N CA 416 417 0.69 -35.00 -35.00
17 4209 62N 63P C N 497 499 -64.16 -64.50 55.08 4.13 -58.70 127.34 10.97
17 63P 63P N CA 499 500 -157.72 147.20 -30.50
18 4210 63P 64P C N 504 506 -56.57 -58.70 25.62 2.29 -64.50 152.37 10.96
18 64P 64P N CA 506 507 -4.97 -30.50 147.20
19 4265 118D 119P C N 942 944 -62.31 -64.50 33.45 2.38 -58.70 144.36 11.64
19 119P 119P N CA 944 945 113.82 147.20 -30.50
20 4266 119P 120N C N 949 951 152.21 -63.20 144.60 21.86 -63.20 144.60 21.86
20 120N 120N N CA 951 952 -40.05 -41.10 -41.10
21 4279 132C 133K C N 1054 1056 -51.86 -62.90 28.36 3.27 -70.20 153.78 11.56
21 133K 133K N CA 1056 1057 -66.92 -40.80 140.40
22 4280 133K 134G C N 1063 1065 -75.53 -62.40 15.75 2.35 82.20 162.98 12.15
22 134G 134G N CA 1065 1066 -32.51 -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 6 16 52 81 131 120 121 181 190 217
<< end of ENERGY.
>> Summary of successfully produced models:
Filename molpdf
----------------------------------------
seq_liganded.B99990001.pdb 921.47980
seq_liganded.B99990002.pdb 1004.99744
Опять получили 2 структуры, посмотрим на обе¶
In [21]:
model_lig_1 = nglview.show_structure_file('seq_liganded.B99990001.pdb')
model_lig_1.clear_representations()
model_lig_1.add_cartoon('protein', color_scheme='residueindex')
model_lig_1.add_ball_and_stick('ligand', opacity=0.5)
model_lig_1
In [46]:
# сравним жабу с форелью синим будет форель, а красным - жаба
show_model("seq_liganded.B99990001.pdb","1lmp.pdb",3 )
In [47]:
# сравним жабу с жабой без лиганда синим будет жаба без лиганда, а красным - жаба с лигандом
show_model("seq_liganded.B99990001.pdb","seq.B99990001.pdb",4 )
In [48]:
model_lig_2 = nglview.show_structure_file('seq_liganded.B99990002.pdb')
model_lig_2.clear_representations()
model_lig_2.add_cartoon('protein', color_scheme='residueindex')
model_lig_2.add_ball_and_stick('ligand', opacity=0.5)
model_lig_2
In [49]:
# сравним жабу с форелью синим будет форель, а красным - жаба
show_model("seq_liganded.B99990002.pdb","1lmp.pdb",5 )
In [50]:
# сравним жабу с жабой без лиганда синим будет жаба без лиганда, а красным - жаба с лигандом
show_model("seq_liganded.B99990002.pdb","seq.B99990002.pdb",6 )
In [51]:
# сравним жабу с жабой без лиганда синим будет жаба без лиганда, а красным - жаба с лигандом
show_model("seq_liganded.B99990001.pdb","seq.B99990002.pdb",6 )
In [52]:
# сравним жабу с жабой без лиганда синим будет жаба без лиганда, а красным - жаба с лигандом
show_model("seq_liganded.B99990002.pdb","seq.B99990001.pdb",6 )
Визуально кажется, что добавление лиганда не сильно изменило конформацию смоделированного белка жабы относительно модели белка без учета лиганда, разве что меняет положение N хвоста¶
Перемещение лиганда¶
Выберем диапазон аминокислот - карман, куда мы попробуем переместить лиганд
In [53]:
model_lig_2
Выберу остатки 48 - 62 в качестве кармана. Это место рядом с основным карманом¶
In [54]:
! rm seq_liganded.rsr
In [55]:
['/',alignm[1].residues[-3],alignm[1].residues[-2],alignm[1].residues[-1]]
Out[55]:
['/', Residue BLK, Residue BLK, Residue BLK]
In [56]:
class mymodel(modeller.automodel.automodel):
def special_restraints(self, aln):
rsr = self.restraints
at = self.atoms
for x,y in [('N:48','O6:147'), ('N:62', 'O6:149')]:
rsr.add(modeller.forms.gaussian(group=modeller.physical.xy_distance,
feature=modeller.features.distance(
at[x],at[y]),mean=3.0, stdev=0.1))
from modeller import *
from modeller.automodel import *
a = mymodel(env, alnfile='all_in_one2.ali', knowns=pdb.code, sequence=s.code)
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()
In [57]:
a.name = 'mod' + s.code
a.starting_model = 1
a.ending_model = 2
a.make()
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: 10 146
atom names : C +N
atom indices : 1164 0
getf_______W> RTF restraint not found in the atoms list:
residue type, indices: 10 146
atom names : C CA +N O
atom indices : 1164 1159 0 1165
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: 14447 13411
iupac_m_397W> Atoms were not swapped because of the uncertainty of how to handle the H atom.
iupac_m_397W> Atoms were not swapped because of the uncertainty of how to handle the H atom.
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 : 149
Number of all, selected real atoms : 1209 1209
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 13411 13411
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 2708
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 : 4921.5029
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 : 1197 6 11 0.024 0.024 197.64 1.000
2 Bond angle potential : 1618 7 24 3.080 3.080 307.79 1.000
3 Stereochemical cosine torsion poten: 814 0 32 47.582 47.582 281.11 1.000
4 Stereochemical improper torsion pot: 502 0 2 1.793 1.793 34.804 1.000
5 Soft-sphere overlap restraints : 2708 2 4 0.010 0.010 34.163 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 7 29 0.365 0.365 367.39 1.000
10 Distance restraints 2 (N-O) : 2564 7 31 0.363 0.363 366.50 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: 145 2 5 7.413 7.413 93.969 1.000
14 Sidechain Chi_1 dihedral restraints: 126 0 3 75.173 75.173 33.294 1.000
15 Sidechain Chi_2 dihedral restraints: 93 0 0 75.255 75.255 39.051 1.000
16 Sidechain Chi_3 dihedral restraints: 37 0 0 79.638 79.638 24.039 1.000
17 Sidechain Chi_4 dihedral restraints: 21 0 0 79.946 79.946 13.504 1.000
18 Disulfide distance restraints : 4 0 0 0.008 0.008 0.46639E-01 1.000
19 Disulfide angle restraints : 8 0 0 1.756 1.756 0.54472 1.000
20 Disulfide dihedral angle restraints: 4 0 0 31.317 31.317 3.6453 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) : 1582 0 0 0.508 0.508 54.444 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: 144 17 17 23.900 61.652 83.970 1.000
26 Distance restraints 4 (SDCH-SDCH) : 744 0 1 0.814 0.814 67.449 1.000
27 Distance restraints 5 (X-Y) : 1403 36 96 0.365 0.365 2918.1 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: seq_liganded.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: 21055.9512
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 1 : Bond length potential
List of the RVIOL violations larger than : 4.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 489 60N 60N C CA 477 472 1.73 1.49 0.24 7.11 1.49 0.24 7.11
2 490 60N 61Y C N 477 479 1.53 1.35 0.19 6.72 1.35 0.19 6.72
3 500 61Y 61Y N CA 479 480 1.67 1.43 0.24 7.88 1.43 0.24 7.88
4 502 61Y 61Y C CA 489 480 1.92 1.49 0.43 12.36 1.49 0.43 12.36
5 503 61Y 62N C N 489 491 1.65 1.35 0.31 10.90 1.35 0.31 10.90
6 508 62N 62N N CA 491 492 1.74 1.43 0.31 10.05 1.43 0.31 10.05
-------------------------------------------------------------------------------------------------
Feature 2 : Bond angle potential
List of the RVIOL violations larger than : 4.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 1727 48A 48A N CA 381 382 123.18 107.00 16.19 4.65 107.00 16.19 4.65
2 1857 60N 60N CA C 472 477 134.84 116.50 18.34 5.27 116.50 18.34 5.27
3 1865 61Y 61Y N CA 479 480 123.92 107.00 16.92 4.86 107.00 16.92 4.86
4 1868 61Y 61Y CA C 480 489 146.79 116.50 30.29 8.71 116.50 30.29 8.71
5 1883 62N 62N N CA 491 492 132.51 107.00 25.51 7.34 107.00 25.51 7.34
-------------------------------------------------------------------------------------------------
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 8128 67S 87P N O 530 712 9.08 6.49 2.59 5.71 6.49 2.59 5.71
-------------------------------------------------------------------------------------------------
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 4148 1S 2G C N 5 7 -78.03 -80.20 2.19 0.15 82.20 -129.37 7.08
1 2G 2G N CA 7 8 174.39 174.10 8.50
2 4149 2G 3K C N 9 11 -66.64 -70.20 5.04 0.30 -62.90 177.66 22.87
2 3K 3K N CA 11 12 136.82 140.40 -40.80
3 4150 3K 4Y C N 18 20 -113.14 -124.30 11.59 0.76 -63.50 -177.46 26.62
3 4Y 4Y N CA 20 21 132.26 135.40 -43.40
4 4152 5I 6S C N 38 40 -67.71 -72.40 5.46 0.44 -64.10 169.84 12.52
4 6S 6S N CA 40 41 155.20 152.40 -35.00
5 4153 6S 7W C N 44 46 -110.44 -124.90 16.86 0.55 -63.00 -174.90 20.87
5 7W 7W N CA 46 47 134.72 143.40 -44.20
6 4154 7W 8E C N 58 60 -82.54 -69.30 24.20 1.40 -63.60 158.08 22.14
6 8E 8E N CA 60 61 162.76 142.50 -40.30
7 4156 9D 10S C N 75 77 -130.12 -136.60 9.68 0.32 -64.10 -169.21 11.77
7 10S 10S N CA 77 78 144.00 151.20 -35.00
8 4158 11C 12S C N 87 89 -70.56 -72.40 55.09 3.18 -64.10 132.50 9.23
8 12S 12S N CA 89 90 97.34 152.40 -35.00
9 4159 12S 13Y C N 93 95 -143.06 -124.30 29.66 1.23 -63.50 177.10 31.98
9 13Y 13Y N CA 95 96 158.38 135.40 -43.40
10 4160 13Y 14L C N 105 107 -87.68 -108.50 32.75 1.50 -63.50 150.39 19.63
10 14L 14L N CA 107 108 107.23 132.50 -41.20
11 4161 14L 15Q C N 113 115 -89.93 -73.00 30.07 2.29 -63.80 158.32 21.99
11 15Q 15Q N CA 115 116 115.85 140.70 -40.30
12 4162 15Q 16L C N 122 124 -121.96 -108.50 24.13 1.37 -63.50 164.41 20.36
12 16L 16L N CA 124 125 112.47 132.50 -41.20
13 4163 16L 17Q C N 130 132 -116.13 -121.10 27.95 1.24 -63.80 161.23 21.36
13 17Q 17Q N CA 132 133 112.20 139.70 -40.30
14 4194 47T 48A C N 379 381 -13.14 -62.50 49.43 9.38 -62.50 49.43 9.38
14 48A 48A N CA 381 382 -43.63 -40.90 -40.90
15 4210 63P 64P C N 504 506 -75.53 -58.70 21.71 1.69 -64.50 164.35 12.85
15 64P 64P N CA 506 507 -16.78 -30.50 147.20
16 4233 86T 87P C N 704 706 -44.27 -58.70 64.76 4.30 -64.50 120.88 10.12
16 87P 87P N CA 706 707 -93.63 -30.50 147.20
17 4234 87P 88R C N 711 713 -96.92 -72.10 64.41 5.43 57.30 160.51 16.29
17 88R 88R N CA 713 714 82.46 141.90 38.00
-------------------------------------------------------------------------------------------------
Feature 27 : Distance restraints 5 (X-Y)
List of the RVIOL violations larger than : 4.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 12063 65D 147. CA C7 514 1173 10.52 9.10 1.42 7.12 9.10 1.42 7.12
2 12064 65D 147. CA O7 514 1179 9.90 8.30 1.60 8.02 8.30 1.60 8.02
3 12065 65D 147. CA N2 514 1180 10.14 8.88 1.25 6.26 8.88 1.25 6.26
4 12066 65D 147. CA O1 514 1181 10.35 9.26 1.09 5.43 9.26 1.09 5.43
5 12374 118D 149. CA O6 937 1208 6.14 5.07 1.07 5.35 5.07 1.07 5.35
6 12389 119P 149. CA O6 945 1208 8.00 6.81 1.19 5.94 6.81 1.19 5.94
7 12578 148. 149. O4 C1 1192 1196 1.62 1.39 0.23 4.64 1.39 0.23 4.64
8 13410 48A 147. N O6 381 1178 7.07 3.00 4.07 40.72 3.00 4.07 40.72
9 13411 62N 149. N O6 491 1208 9.96 3.00 6.96 69.57 3.00 6.96 69.57
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 15 18 74 82 135 137 158 186 216 213
<< end of ENERGY.
iupac_m_397W> Atoms were not swapped because of the uncertainty of how to handle the H atom.
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 : 149
Number of all, selected real atoms : 1209 1209
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 13411 13411
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 2716
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 : 4809.3828
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 : 1197 6 10 0.024 0.024 197.41 1.000
2 Bond angle potential : 1618 6 23 3.085 3.085 308.94 1.000
3 Stereochemical cosine torsion poten: 814 0 32 47.914 47.914 282.89 1.000
4 Stereochemical improper torsion pot: 502 1 1 1.801 1.801 34.385 1.000
5 Soft-sphere overlap restraints : 2716 2 4 0.010 0.010 34.547 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 6 30 0.363 0.363 360.41 1.000
10 Distance restraints 2 (N-O) : 2564 6 22 0.341 0.341 324.92 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: 145 2 6 7.392 7.392 93.426 1.000
14 Sidechain Chi_1 dihedral restraints: 126 0 0 65.712 65.712 19.654 1.000
15 Sidechain Chi_2 dihedral restraints: 93 0 0 69.460 69.460 30.178 1.000
16 Sidechain Chi_3 dihedral restraints: 37 0 0 79.700 79.700 21.946 1.000
17 Sidechain Chi_4 dihedral restraints: 21 0 0 73.356 73.356 10.121 1.000
18 Disulfide distance restraints : 4 0 0 0.007 0.007 0.34899E-01 1.000
19 Disulfide angle restraints : 8 0 0 2.820 2.820 1.4045 1.000
20 Disulfide dihedral angle restraints: 4 0 0 23.157 23.157 2.1662 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) : 1582 0 0 0.461 0.461 41.107 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: 144 16 14 22.716 60.929 70.963 1.000
26 Distance restraints 4 (SDCH-SDCH) : 744 0 0 0.744 0.744 54.279 1.000
27 Distance restraints 5 (X-Y) : 1403 36 96 0.363 0.363 2920.6 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: seq_liganded.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: 20051.7246
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 1 : Bond length potential
List of the RVIOL violations larger than : 4.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 489 60N 60N C CA 477 472 1.73 1.49 0.24 6.85 1.49 0.24 6.85
2 490 60N 61Y C N 477 479 1.52 1.35 0.18 6.36 1.35 0.18 6.36
3 500 61Y 61Y N CA 479 480 1.66 1.43 0.23 7.53 1.43 0.23 7.53
4 502 61Y 61Y C CA 489 480 1.93 1.49 0.44 12.84 1.49 0.44 12.84
5 503 61Y 62N C N 489 491 1.66 1.35 0.32 11.28 1.35 0.32 11.28
6 508 62N 62N N CA 491 492 1.73 1.43 0.30 9.77 1.43 0.30 9.77
-------------------------------------------------------------------------------------------------
Feature 2 : Bond angle potential
List of the RVIOL violations larger than : 4.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 1727 48A 48A N CA 381 382 123.38 107.00 16.38 4.71 107.00 16.38 4.71
2 1857 60N 60N CA C 472 477 134.39 116.50 17.89 5.14 116.50 17.89 5.14
3 1868 61Y 61Y CA C 480 489 148.21 116.50 31.71 9.12 116.50 31.71 9.12
4 1883 62N 62N N CA 491 492 132.45 107.00 25.45 7.32 107.00 25.45 7.32
-------------------------------------------------------------------------------------------------
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 4148 1S 2G C N 5 7 -78.05 -80.20 3.20 0.10 82.20 -131.25 7.08
1 2G 2G N CA 7 8 171.74 174.10 8.50
2 4149 2G 3K C N 9 11 -62.30 -70.20 8.06 0.62 -62.90 177.17 22.98
2 3K 3K N CA 11 12 142.03 140.40 -40.80
3 4150 3K 4Y C N 18 20 -116.26 -124.30 8.21 0.56 -63.50 -175.22 26.84
3 4Y 4Y N CA 20 21 133.68 135.40 -43.40
4 4152 5I 6S C N 38 40 -65.10 -72.40 7.43 0.57 -64.10 171.18 12.46
4 6S 6S N CA 40 41 153.82 152.40 -35.00
5 4153 6S 7W C N 44 46 -116.27 -124.90 14.04 0.81 -63.00 169.89 24.79
5 7W 7W N CA 46 47 154.48 143.40 -44.20
6 4154 7W 8E C N 58 60 -77.72 -69.30 17.55 1.05 -63.60 162.41 22.44
6 8E 8E N CA 60 61 157.90 142.50 -40.30
7 4156 9D 10S C N 75 77 -131.02 -136.60 5.71 0.20 -64.10 -172.62 18.30
7 10S 10S N CA 77 78 149.98 151.20 -35.00
8 4158 11C 12S C N 87 89 -72.49 -72.40 25.18 1.48 -64.10 162.44 11.30
8 12S 12S N CA 89 90 127.22 152.40 -35.00
9 4159 12S 13Y C N 93 95 -136.79 -124.30 21.88 0.88 -63.50 178.93 32.01
9 13Y 13Y N CA 95 96 153.37 135.40 -43.40
10 4160 13Y 14L C N 105 107 -86.62 -108.50 45.64 2.19 -63.50 135.64 17.64
10 14L 14L N CA 107 108 92.45 132.50 -41.20
11 4161 14L 15Q C N 113 115 -105.03 -121.10 21.29 0.68 -63.80 171.09 23.20
11 15Q 15Q N CA 115 116 125.74 139.70 -40.30
12 4162 15Q 16L C N 122 124 -130.99 -108.50 24.55 1.09 -63.50 -171.08 30.41
12 16L 16L N CA 124 125 142.35 132.50 -41.20
13 4163 16L 17Q C N 130 132 -133.63 -121.10 12.53 0.47 -63.80 -167.10 25.33
13 17Q 17Q N CA 132 133 139.51 139.70 -40.30
14 4194 47T 48A C N 379 381 -13.74 -62.50 48.80 9.29 -62.50 48.80 9.29
14 48A 48A N CA 381 382 -43.03 -40.90 -40.90
15 4198 51E 52S C N 414 416 -138.41 -64.10 81.75 8.67 -64.10 81.75 8.67
15 52S 52S N CA 416 417 -0.90 -35.00 -35.00
16 4210 63P 64P C N 504 506 -76.18 -58.70 22.01 1.77 -64.50 164.73 12.92
16 64P 64P N CA 506 507 -17.12 -30.50 147.20
-------------------------------------------------------------------------------------------------
Feature 27 : Distance restraints 5 (X-Y)
List of the RVIOL violations larger than : 4.5000
# ICSR RESNO1/2 ATM1/2 INDATM1/2 FEAT restr viol rviol RESTR VIOL RVIOL
1 12063 65D 147. CA C7 514 1173 10.41 9.10 1.32 6.58 9.10 1.32 6.58
2 12064 65D 147. CA O7 514 1179 9.79 8.30 1.50 7.49 8.30 1.50 7.49
3 12065 65D 147. CA N2 514 1180 10.03 8.88 1.15 5.74 8.88 1.15 5.74
4 12066 65D 147. CA O1 514 1181 10.25 9.26 0.99 4.96 9.26 0.99 4.96
5 12374 118D 149. CA O6 937 1208 6.13 5.07 1.06 5.31 5.07 1.06 5.31
6 12389 119P 149. CA O6 945 1208 7.99 6.81 1.18 5.88 6.81 1.18 5.88
7 12578 148. 149. O4 C1 1192 1196 1.63 1.39 0.24 4.76 1.39 0.24 4.76
8 13410 48A 147. N O6 381 1178 7.08 3.00 4.08 40.79 3.00 4.08 40.79
9 13411 62N 149. N O6 491 1208 10.01 3.00 7.01 70.08 3.00 7.01 70.08
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 14 17 75 85 136 135 160 195 209 229
<< end of ENERGY.
>> Summary of successfully produced models:
Filename molpdf
----------------------------------------
seq_liganded.B99990001.pdb 4921.50293
seq_liganded.B99990002.pdb 4809.38281
In [58]:
model_new_lig = nglview.show_structure_file('seq_liganded.B99990001.pdb')
model_new_lig.clear_representations()
model_new_lig.add_cartoon('protein', color_scheme='residueindex')
model_new_lig.add_ball_and_stick('ligand', opacity=0.5)
model_new_lig
In [59]:
# сравним жабу с форелью синим будет форель, а красным - жаба
show_model("seq_liganded.B99990001.pdb","1lmp.pdb",7 )
In [62]:
# сравним жабу с форелью синим будет форель, а красным - жаба
show_model("seq_liganded.B99990002.pdb","1lmp.pdb",7 )
Modeller конечно не позволил переместить лиганд. Не заметно, что он хоть как то изменил структуру смоделированноо жабьего белка относительно его модели построенной без подвижек лиганда. Зато заметно что сам лиганд немного поменят конформацию относительно белка форели
Аланиновый лизоцим¶
In [64]:
len(alignm[1])
Out[64]:
149
In [ ]:
# 132 остатка в 1lmp
In [65]:
alignm = modeller.alignment(env)
mdl = modeller.model(env, file='1lmp.pdb', model_segment=('FIRST:'+'A', 'LAST:'+'B'))
alignm.append_model(mdl, atom_files='1lmp.pdb', align_codes='1lmp')
seq_ala = 'A' * 146 + '...'
alignm.append_sequence(seq_ala)
alignm[0].code = 'pdb'
alignm[1].code = 'seq_ala'
In [66]:
alignm.salign()
alignm.write(file='all_in_one3.ali', alignment_format='PIR')
SALIGN_____> adding the next group to the alignment; iteration 1
In [67]:
! cat all_in_one3.ali
>P1;pdb structureX:1lmp.pdb: 1 :A:+132 :B: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 KVYDRCELARALKASGMDGYAGNSLPNWVCLSKWESSYNTQATNRNTDGSTDYGIFQINSRY------------- ----WCDDGRTPGAKNVCGIRCSQLLTDDLTVAIRCAKRVVLDPNGIGAWVAWRLHCQNQDLRSYVAGCGV/...* >P1;seq_ala sequence::1 : :+149 : :undefined:undefined:-1.00:-1.00 AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA-...*
In [68]:
s = alignm[1]
pdb = alignm[0]
print(s.code, pdb.code)
a = modeller.automodel.automodel(env, alnfile='all_in_one3.ali', knowns=pdb.code, sequence=s.code)
a.name = 'mod' + s.code
a.starting_model = 1
a.ending_model = 2
a.make()
seq_ala pdb
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: 1 146
atom names : C +N
atom indices : 729 0
getf_______W> RTF restraint not found in the atoms list:
residue type, indices: 1 146
atom names : C CA +N O
atom indices : 729 727 0 730
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.)
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: 10506 9783
>> ENERGY; Differences between the model's features and restraints:
Number of all residues in MODEL : 149
Number of all, selected real atoms : 774 774
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 9783 9783
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 1491
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 : 762.1390
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 : 730 0 0 0.007 0.007 10.689 1.000
2 Bond angle potential : 1021 1 8 2.345 2.345 115.02 1.000
3 Stereochemical cosine torsion poten: 296 0 47 80.007 80.007 308.48 1.000
4 Stereochemical improper torsion pot: 292 0 1 1.246 1.246 12.659 1.000
5 Soft-sphere overlap restraints : 1491 2 3 0.013 0.013 27.923 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 0.251 0.251 61.512 1.000
10 Distance restraints 2 (N-O) : 2564 1 2 0.333 0.333 107.37 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: 145 1 4 5.209 5.209 46.392 1.000
14 Sidechain Chi_1 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
15 Sidechain Chi_2 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
16 Sidechain Chi_3 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
17 Sidechain Chi_4 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
18 Disulfide distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
19 Disulfide angle restraints : 0 0 0 0.000 0.000 0.0000 1.000
20 Disulfide dihedral angle restraints: 0 0 0 0.000 0.000 0.0000 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) : 722 0 0 0.228 0.228 4.4656 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: 144 34 19 30.054 85.796 37.107 1.000
26 Distance restraints 4 (SDCH-SDCH) : 63 0 0 0.545 0.545 1.7018 1.000
27 Distance restraints 5 (X-Y) : 1401 0 0 0.050 0.050 28.813 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: seq_ala.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: 15910.8486
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 6626 93A 80A N O 461 400 4.79 2.92 1.87 4.68 2.92 1.87 4.68
-------------------------------------------------------------------------------------------------
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 2354 15A 16A C N 74 76 77.89 55.40 26.72 1.88 -62.50 154.57 31.40
1 16A 16A N CA 76 77 23.78 38.20 -40.90
2 2357 18A 19A C N 89 91 65.75 55.40 24.89 0.90 -62.50 140.13 28.45
2 19A 19A N CA 91 92 15.57 38.20 -40.90
3 2359 20A 21A C N 99 101 54.24 55.40 4.63 0.37 -62.50 138.55 28.15
3 21A 21A N CA 101 102 33.71 38.20 -40.90
4 2360 21A 22A C N 104 106 61.92 55.40 8.69 0.50 -62.50 144.42 29.37
4 22A 22A N CA 106 107 32.45 38.20 -40.90
5 2375 36A 37A C N 179 181 66.15 55.40 13.21 0.87 -62.50 147.15 29.93
5 37A 37A N CA 181 182 30.53 38.20 -40.90
6 2376 37A 38A C N 184 186 61.62 55.40 10.16 0.44 -62.50 143.02 29.09
6 38A 38A N CA 186 187 30.16 38.20 -40.90
7 2387 48A 49A C N 239 241 84.41 55.40 37.50 2.27 -62.50 156.99 31.78
7 49A 49A N CA 241 242 14.44 38.20 -40.90
8 2392 53A 54A C N 264 266 93.31 -134.00 137.11 3.41 -62.50 -152.16 32.59
8 54A 54A N CA 266 267 -178.45 147.00 -40.90
9 2395 56A 57A C N 279 281 58.00 55.40 17.42 1.27 -62.50 154.27 31.17
9 57A 57A N CA 281 282 55.42 38.20 -40.90
10 2401 62A 63A C N 309 311 -77.40 -68.20 11.64 0.75 -62.50 167.33 28.18
10 63A 63A N CA 311 312 152.43 145.30 -40.90
11 2402 63A 64A C N 314 316 -148.74 -134.00 14.77 0.52 -62.50 -166.68 36.30
11 64A 64A N CA 316 317 146.08 147.00 -40.90
12 2403 64A 65A C N 319 321 -151.48 -134.00 19.73 1.00 -62.50 -160.32 29.93
12 65A 65A N CA 321 322 137.85 147.00 -40.90
13 2404 65A 66A C N 324 326 160.97 -134.00 72.37 1.65 -62.50 -164.20 39.05
13 66A 66A N CA 326 327 178.75 147.00 -40.90
14 2405 66A 67A C N 329 331 -69.13 -68.20 4.66 0.41 -62.50 178.49 29.58
14 67A 67A N CA 331 332 140.73 145.30 -40.90
15 2406 67A 68A C N 334 336 171.77 -134.00 56.15 1.39 -62.50 -158.42 39.60
15 68A 68A N CA 336 337 161.55 147.00 -40.90
16 2407 68A 69A C N 339 341 -116.30 -134.00 27.76 0.93 -62.50 174.99 26.61
16 69A 69A N CA 341 342 125.61 147.00 -40.90
17 2408 69A 70A C N 344 346 -133.71 -134.00 10.30 0.58 -62.50 -168.65 28.85
17 70A 70A N CA 346 347 136.71 147.00 -40.90
18 2409 70A 71A C N 349 351 69.57 -68.20 139.71 12.58 -62.50 -159.71 30.58
18 71A 71A N CA 351 352 168.52 145.30 -40.90
19 2410 71A 72A C N 354 356 -104.47 -134.00 39.99 1.14 -62.50 166.30 25.54
19 72A 72A N CA 356 357 120.02 147.00 -40.90
20 2411 72A 73A C N 359 361 163.41 -134.00 65.44 1.57 -62.50 -156.54 40.27
20 73A 73A N CA 361 362 166.08 147.00 -40.90
21 2412 73A 74A C N 364 366 -103.96 -134.00 44.20 1.39 -62.50 160.91 24.69
21 74A 74A N CA 366 367 114.58 147.00 -40.90
22 2413 74A 75A C N 369 371 166.91 -134.00 61.48 1.50 -62.50 -157.21 40.01
22 75A 75A N CA 371 372 163.96 147.00 -40.90
23 2414 75A 76A C N 374 376 -115.11 -134.00 34.23 1.29 -62.50 167.81 25.50
23 76A 76A N CA 376 377 118.45 147.00 -40.90
24 2415 76A 77A C N 379 381 -150.74 -134.00 17.16 0.71 -62.50 -163.23 36.97
24 77A 77A N CA 381 382 143.23 147.00 -40.90
25 2416 77A 78A C N 384 386 -176.00 -134.00 44.39 2.03 -62.50 -152.63 31.14
25 78A 78A N CA 386 387 132.65 147.00 -40.90
26 2417 78A 79A C N 389 391 -179.53 -134.00 50.50 2.51 -62.50 -156.86 30.58
26 79A 79A N CA 391 392 125.14 147.00 -40.90
27 2422 83A 84A C N 414 416 75.34 55.40 54.64 2.01 -62.50 140.70 28.03
27 84A 84A N CA 416 417 -12.67 38.20 -40.90
28 2426 87A 88A C N 434 436 53.26 55.40 12.21 0.57 -62.50 147.31 29.78
28 88A 88A N CA 436 437 50.22 38.20 -40.90
29 2429 90A 91A C N 449 451 57.81 55.40 19.84 1.39 -62.50 155.67 31.42
29 91A 91A N CA 451 452 57.89 38.20 -40.90
30 2432 93A 94A C N 464 466 61.15 55.40 23.66 1.90 -62.50 160.32 32.35
30 94A 94A N CA 466 467 61.15 38.20 -40.90
31 2459 120A 121A C N 599 601 79.13 -134.00 161.28 3.66 -62.50 176.58 28.30
31 121A 121A N CA 601 602 -146.37 147.00 -40.90
32 2472 133A 134A C N 664 666 47.39 55.40 16.12 0.60 -62.50 144.02 29.03
32 134A 134A N CA 666 667 52.19 38.20 -40.90
33 2481 142A 143A C N 709 711 71.97 55.40 43.48 1.59 -62.50 139.98 28.15
33 143A 143A N CA 711 712 -2.00 38.20 -40.90
34 2483 144A 145A C N 719 721 62.03 55.40 8.10 0.54 -62.50 145.09 29.50
34 145A 145A N CA 721 722 33.55 38.20 -40.90
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 2 6 7 55 59 82 80 87 127 122 88
<< end of ENERGY.
>> ENERGY; Differences between the model's features and restraints:
Number of all residues in MODEL : 149
Number of all, selected real atoms : 774 774
Number of all, selected pseudo atoms : 0 0
Number of all static, selected restraints : 9783 9783
COVALENT_CYS : F
NONBONDED_SEL_ATOMS : 1
Number of non-bonded pairs (excluding 1-2,1-3,1-4): 1389
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 : 724.2225
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 : 730 0 0 0.006 0.006 6.9255 1.000
2 Bond angle potential : 1021 0 6 2.180 2.180 97.640 1.000
3 Stereochemical cosine torsion poten: 296 0 42 79.629 79.629 302.34 1.000
4 Stereochemical improper torsion pot: 292 0 1 1.391 1.391 12.715 1.000
5 Soft-sphere overlap restraints : 1389 1 2 0.011 0.011 21.663 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 0.237 0.237 51.994 1.000
10 Distance restraints 2 (N-O) : 2564 0 3 0.333 0.333 99.539 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: 145 0 4 4.643 4.643 36.869 1.000
14 Sidechain Chi_1 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
15 Sidechain Chi_2 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
16 Sidechain Chi_3 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
17 Sidechain Chi_4 dihedral restraints: 0 0 0 0.000 0.000 0.0000 1.000
18 Disulfide distance restraints : 0 0 0 0.000 0.000 0.0000 1.000
19 Disulfide angle restraints : 0 0 0 0.000 0.000 0.0000 1.000
20 Disulfide dihedral angle restraints: 0 0 0 0.000 0.000 0.0000 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) : 722 0 0 0.241 0.241 4.8932 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: 144 36 21 32.016 85.189 70.938 1.000
26 Distance restraints 4 (SDCH-SDCH) : 63 0 0 0.497 0.497 1.3982 1.000
27 Distance restraints 5 (X-Y) : 1401 0 0 0.037 0.037 17.306 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: seq_ala.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: 15729.5527
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 2354 15A 16A C N 74 76 77.54 55.40 25.44 1.90 -62.50 155.05 31.51
1 16A 16A N CA 76 77 25.67 38.20 -40.90
2 2357 18A 19A C N 89 91 64.69 55.40 21.60 0.78 -62.50 140.46 28.54
2 19A 19A N CA 91 92 18.70 38.20 -40.90
3 2359 20A 21A C N 99 101 53.26 55.40 4.49 0.44 -62.50 138.01 28.04
3 21A 21A N CA 101 102 34.25 38.20 -40.90
4 2360 21A 22A C N 104 106 59.51 55.40 4.35 0.39 -62.50 144.64 29.39
4 22A 22A N CA 106 107 36.79 38.20 -40.90
5 2375 36A 37A C N 179 181 66.94 55.40 14.39 0.93 -62.50 147.38 29.97
5 37A 37A N CA 181 182 29.59 38.20 -40.90
6 2376 37A 38A C N 184 186 62.18 55.40 9.93 0.50 -62.50 143.90 29.26
6 38A 38A N CA 186 187 30.95 38.20 -40.90
7 2387 48A 49A C N 239 241 84.06 55.40 39.21 2.17 -62.50 155.63 31.46
7 49A 49A N CA 241 242 11.45 38.20 -40.90
8 2392 53A 54A C N 264 266 92.68 -134.00 138.23 3.40 -62.50 -153.92 32.35
8 54A 54A N CA 266 267 -176.50 147.00 -40.90
9 2395 56A 57A C N 279 281 59.67 55.40 14.46 1.22 -62.50 153.48 31.06
9 57A 57A N CA 281 282 52.02 38.20 -40.90
10 2400 61A 62A C N 304 306 -46.54 -62.50 41.72 7.69 -62.50 41.72 7.69
10 62A 62A N CA 306 307 -2.35 -40.90 -40.90
11 2401 62A 63A C N 309 311 -46.63 -68.20 31.34 1.97 -62.50 164.24 27.72
11 63A 63A N CA 311 312 122.57 145.30 -40.90
12 2402 63A 64A C N 314 316 128.80 -134.00 98.23 3.81 -62.50 -117.88 37.32
12 64A 64A N CA 316 317 132.78 147.00 -40.90
13 2403 64A 65A C N 319 321 159.92 -134.00 72.52 1.65 -62.50 -162.11 39.45
13 65A 65A N CA 321 322 176.86 147.00 -40.90
14 2404 65A 66A C N 324 326 -143.52 -134.00 10.29 0.49 -62.50 -166.24 36.09
14 66A 66A N CA 326 327 143.10 147.00 -40.90
15 2405 66A 67A C N 329 331 175.80 -134.00 52.41 1.26 -62.50 -161.31 38.93
15 67A 67A N CA 331 332 162.05 147.00 -40.90
16 2406 67A 68A C N 334 336 -80.13 -68.20 13.20 0.92 -62.50 169.07 28.61
16 68A 68A N CA 336 337 150.96 145.30 -40.90
17 2407 68A 69A C N 339 341 -73.76 -68.20 5.56 0.47 -62.50 174.00 29.08
17 69A 69A N CA 341 342 145.47 145.30 -40.90
18 2408 69A 70A C N 344 346 -72.33 -68.20 11.39 0.78 -62.50 163.48 27.28
18 70A 70A N CA 346 347 155.92 145.30 -40.90
19 2409 70A 71A C N 349 351 -80.64 -68.20 36.23 3.33 -62.50 153.25 24.29
19 71A 71A N CA 351 352 111.28 145.30 -40.90
20 2410 71A 72A C N 354 356 159.51 -134.00 67.50 1.83 -62.50 -148.38 41.83
20 72A 72A N CA 356 357 158.65 147.00 -40.90
21 2411 72A 73A C N 359 361 -73.89 -68.20 8.22 0.81 -62.50 -179.91 30.09
21 73A 73A N CA 361 362 139.37 145.30 -40.90
22 2412 73A 74A C N 364 366 -145.51 -134.00 12.38 0.59 -62.50 -164.80 36.44
22 74A 74A N CA 366 367 142.43 147.00 -40.90
23 2413 74A 75A C N 369 371 -160.12 -134.00 26.18 0.80 -62.50 -163.59 37.40
23 75A 75A N CA 371 372 148.67 147.00 -40.90
24 2414 75A 76A C N 374 376 175.22 -134.00 55.46 1.26 -62.50 -166.60 38.06
24 76A 76A N CA 376 377 169.27 147.00 -40.90
25 2415 76A 77A C N 379 381 -121.20 -134.00 14.15 0.32 -62.50 -172.44 33.87
25 77A 77A N CA 381 382 140.97 147.00 -40.90
26 2416 77A 78A C N 384 386 164.60 -134.00 73.67 1.79 -62.50 -173.12 37.36
26 78A 78A N CA 386 387 -172.28 147.00 -40.90
27 2417 78A 79A C N 389 391 -139.27 -134.00 100.81 5.60 -62.50 104.86 21.04
27 79A 79A N CA 391 392 -112.33 147.00 -40.90
28 2422 83A 84A C N 414 416 79.74 55.40 59.23 2.14 -62.50 144.44 28.66
28 84A 84A N CA 416 417 -15.79 38.20 -40.90
29 2426 87A 88A C N 434 436 50.45 55.40 22.45 0.98 -62.50 151.51 30.46
29 88A 88A N CA 436 437 60.09 38.20 -40.90
30 2429 90A 91A C N 449 451 68.48 55.40 13.71 1.62 -62.50 155.18 31.53
30 91A 91A N CA 451 452 42.31 38.20 -40.90
31 2432 93A 94A C N 464 466 63.07 55.40 11.33 1.26 -62.50 153.01 31.04
31 94A 94A N CA 466 467 46.54 38.20 -40.90
32 2459 120A 121A C N 599 601 80.66 -134.00 159.97 3.63 -62.50 177.69 28.52
32 121A 121A N CA 601 602 -146.16 147.00 -40.90
33 2472 133A 134A C N 664 666 49.91 55.40 12.12 0.44 -62.50 143.93 29.08
33 134A 134A N CA 666 667 49.00 38.20 -40.90
34 2480 141A 142A C N 704 706 58.65 -68.20 133.45 12.53 -68.20 133.45 12.53
34 142A 142A N CA 706 707 -173.24 145.30 145.30
35 2481 142A 143A C N 709 711 -81.52 -68.20 73.04 6.35 -62.50 115.95 18.16
35 143A 143A N CA 711 712 73.48 145.30 -40.90
36 2483 144A 145A C N 719 721 65.07 55.40 13.09 0.74 -62.50 145.65 29.62
36 145A 145A N CA 721 722 29.38 38.20 -40.90
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 4 9 46 52 73 80 91 122 100 103
<< end of ENERGY.
>> Summary of successfully produced models:
Filename molpdf
----------------------------------------
seq_ala.B99990001.pdb 762.13904
seq_ala.B99990002.pdb 724.22253
In [69]:
w_ala = nglview.show_structure_file('seq_ala.B99990001.pdb')
w_ala.clear_representations()
w_ala.add_cartoon('protein', color_scheme='residueindex')
w_ala.add_ball_and_stick('ligand', opacity=0.5)
w_ala
In [71]:
# сравним жабу с форелью синим будет форель, а красным - поли-аланин
show_model("seq_ala.B99990001.pdb","1lmp.pdb",8 )
Modeller в отличии от человека не умеет критически мыслить и может построить нужную структуру по более менее любой последовательности, если она хоть как то выравнивается с целевой. Поэтому нужно хорошо думать прежде чем моделировать таким образом.
Сравним скор функцию¶
In [73]:
pd.DataFrame({"нет лиганда":[780.65515,801.29517],
"лиганд":[ 921.47980,1004.99744],
"сдвинутый лиганд":[4921.50293,4809.38281],
"полиаланиновый псевдобелок":[762.13904,724.22253]})
# чем меньше скор - тем лучше
Out[73]:
| нет лиганда | лиганд | сдвинутый лиганд | полиаланиновый псевдобелок | |
|---|---|---|---|---|
| 0 | 780.65515 | 921.47980 | 4921.50293 | 762.13904 |
| 1 | 801.29517 | 1004.99744 | 4809.38281 | 724.22253 |
Забавно, что самыми хорошими моделями оказываются полиаланиновые псевдобелки. Вторыми по качеству оказываются белки без лиганда, третьими белки с лигандом. Самыми последними с большим отставанием по скору идут белки со сдвинутым лигандом. Плохой скор белков со сдвинутым лиандом логичен, ведь мы пытались привести белок в несвойственное ему состояние. Порядок (по скору) остальных трех групп по видимому варьируется в зависимости от белка. Стоит понимать, что даже моделирование структуры на основании тупой полиаланиновой цепи может привести к хорошим результатам и относиться к результатам моделирования с оснорожностью и вдумчивостью.