Validation of the prepared protein structure models

The prepared protein structure models were validated by docking the corresponding native ligands (derived from the available liganded PDB structures of the same protein) and analyzing the correctness of ligand placement using the RMSD criterion. If the predicted ligand pose was within 2 Å from the corresponding crystallographic position, the ligand was regarded as correctly docked. The single protein structure model was considered satisfactory for virtual screening if all its cognate ligands could be correctly docked this single model.

The following ligands were used for the validation of the developed protein structure models:

ADRB2

Ligand / pdb ID
(2S)-1-(9H-Carbazol-4-yloxy)-3-(isopropylamino)propan- 2-ol / 2rh1
(2S)-1-(tert-butylamino)-3-[(4-morpholin- 4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol / 3d4s

Conclusion: all ligands were docked correctly to the model prepared from 2rh1

DHFR

Ligand / pdb ID
n6-(2,5-dimethoxy-benzyl)-n6-methyl-pyrido[2,3- d]pyrimidine-2,4,6-triamine / 1boz
folic acid / 1dhf
6-(2,5-dimethoxy-benzyl)-5-methyl-pyrido[2,3- d]pyrimidine-2,4-diamine / 1dlr
methotrexate / 1dls
n-[4-[(2,4-diaminofuro[2,3d]pyrimidin-5-yl)methyl]methylamino]- benzoyl]-l-glutamate / 1hfp
6-([5-quinolylamino]methyl)-2,4-diamino-5- methylpyrido[2,3-d]pyrimidine / 1kms
(z)-6-(2-[2,5-dimethoxyphenyl]ethen-1-yl)- 2,4-diamino-5-methylpyrido[2,3-d]pyrimidine / 1kmv
2,4-diamino-6-[n-(3',4',5'-trimethoxybenzyl)- n-methylamino]pyrido[2,3-d]pyrimidine / 1mvs
2,4-diamino-5-methyl-6-[(3,4,5-trimethoxy- n-methylanilino)methyl]pyrido[2,3-d]pyrimidine / 1pd8
6-{[methyl(3,4,5-trimethoxycyclohexyl)amino]methyl}decahydroquinazoline- 2,4-diamine / 1s3u
6-(octahydro-1h-indol-1-ylmethyl)decahydroquinazoline- 2,4-diamine / 1s3w
5-deazafolic acid / 2dhf
n-(4-carboxy-4-{4-[(2,4-diamino-pteridin- 6-ylmethyl)-amino]-benzoylamino}-butyl)-phthalamic acid / 1ohj
n6-(2,5-dimethoxy-benzyl)-n6-methyl-pyrido[2,3- d]pyrimidine-2,4,6-triamine / 1boz

Conclusion: all ligands were docked correctly to the model prepared from 1dls

DHODH

Ligand / pdb ID
2-biphenyl-4-yl-6-fluoro-3-methyl-quinoline- 4-carboxylic acid / 1d3g
2-cyano-3-hydroxy-n-(4-trifluoromethyl-phenyl)- butyramide / 1d3h
3-amido-5-biphenyl-benzoic acid / 2b0m
2-({[3-fluoro-3'-(trifluoromethoxy)biphenyl- 4-yl]amino}carbonyl)cyclopent-1-ene-1-carboxylic acid / 2bxv
2-({[3,5-difluoro-3'-(trifluoromethoxy)biphenyl- 4-yl]amino}carbonyl)cyclopent-1-ene-1-carboxylic acid / 2fpt
3-{[(3-fluoro-3'-methoxybiphenyl-4-yl)amino]carbonyl}thiophene- 2-carboxylic acid / 2fpv
3-({[3,5-difluoro-3'-(trifluoromethoxy)biphenyl- 4-yl]amino}carbonyl)thiophene-2-carboxylic acid / 2fpy
2-({[2,3,5,6-tetrafluoro-3'-(trifluoromethoxy)biphenyl- 4-yl]amino}carbonyl)cyclopenta-1,3-diene- 1-carboxylic acid / 2fqi

Conclusion: all ligands were docked correctly to the model prepared from 2fqi

HMG-CoAR

Ligand / pdb ID
(3R,5R)-7-[2-(4-fluorophenyl)-5-(1-methylethyl)- 4-(morpholin-4-ylsulfonyl)-3-phenyl-1H-pyrrol- 1-yl]-3,5-dihydroxyheptanoic / 3bgl
(3R,5R)-7-[1-(4-fluorophenyl)-4-(1-methylethyl)- 3-{methyl[(1R)-1-phenylethyl]carbamoyl}-1H- pyrazol-5-yl]-3,5-dihydroxyheptanoic acid / 2r4f
(3r,5r)-7-[1-(4-fluorophenyl)-3-isopropyl- 4-oxo-5-phenyl-4,5-dihydro-3h-pyrrolo[2,3- c]quinolin-2-yl]-3,5-dihydroxyheptanoic acid / 2q6c
(3r,5r)-7-[3-(4-fluorophenyl)-1-isopropyl- 8-oxo-7-phenyl-1,4,5,6,7,8-hexahydropyrrolo[2,3- c]azepin-2-yl]-3,5-dihydroxyheptanoic acid / 2q6b
(3r,5r)-7-[5-(anilinocarbonyl)-3,4-bis(4- fluorophenyl)-1-isopropyl-1h-pyrrol-2-yl]- 3,5-dihydroxyheptanoic acid / 2q1l
7-[4-(4-fluoro-phenyl)-6-isopropyl-2-(methanesulfonyl- methyl-amino)-pyrimidin-5-yl] -3,5-dihydroxy- heptanoic acid / 1hwl
7-[2-(4-fluoro-phenyl)-5-isopropyl-3-phenyl- 4-phenylcarbamoyl-pyrrol-1-yl]- 3,5-dihydroxy- heptanoic acid / 1hwk
7-[4-(4-fluoro-phenyl)-5-hydroxymethyl-2,6- diisopropyl-pyridin-3-yl]-3,5-dihydroxy-heptanoic acid / 1hwj
7-[3-(4-fluoro-phenyl)-1-isopropyl-1h-indol- 2-yl]-3,5-dihydroxy-heptanoic acid / 1hwi
simvastatin / 1hw9
compactin / 1hw8

Conclusion: all ligands were docked correctly to the model prepared from 1hwl

LTA4H

Ligand / pdb ID
2-(3-amino-2-hydroxy-4-phenyl-butyrylamino)- 4-methyl-pentanoic acid / 1gw6
6-[{(2s)-2-amino-3-[4-(benzyloxy)phenyl]propyl}(hydroxy)amino]- 6-oxohexanoic acid) / 2vj8
n-[4-(benzyloxy)phenyl]glycinamide / 3cho
(3s)-3-amino-4-oxo-4-[(4-phenylmethoxyphenyl)amino]butanoic acid / 3chp
(2s)-2-amino-5-oxo-5-[(4-phenylmethoxyphenyl)amino]pentanoic acid / 3chq
4-amino-n-[4-(benzyloxy)phenyl]butanamide / 3chr
(2s)-2-amino-5-[[4-[(2s)-2-hydroxy-2-phenyl- ethoxy]phenyl]amino]-5-oxo-pentanoic acid / 3chs

Conclusion: all ligands were docked correctly to the model prepared from 2vj8

mGluR3

Ligand / pdb ID
(1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid / 2e4w
(1S,3R)- 1-aminocyclopentane-1,3-dicarboxylic acid / 2e4x
(2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid / 2e4y
(1R,2R)-3-[(S)-amino(carboxy)methyl]cyclopropane- 1,2-dicarboxylic acid / 2e4v
Glutamic acid / 2e4u

Conclusion: all ligands were docked correctly to the model prepared from 2e4w

OMPDC

Ligand / pdb ID
6-hydroxyuridine-5'-phosphate / 1jjk
1-(5'-phospho-beta-d-ribofuranosyl)barbituric acid / 1eix

Conclusion: all ligands were docked correctly to the model prepared from 1eix

PPAR-g

Ligand / pdb ID
2-(2-benzoyl-phenylamino)-3-{4-[2-(5-methyl- 2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid / 1fm9
(2s)-2-ethoxy-3-[4-(2-{4-[(methylsulfonyl)oxy]phenyl}ethoxy)phenyl]propanoic acid / 1i7i
2-(1-methyl-3-oxo-3-phenyl-propylamino)-3- {4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]- phenyl}-propionic acid / 1k74
(s)-3-(4-(2-carbazol-9-yl-ethoxy)-phenyl)- 2-ethoxy-propionic acid / 1knu
(2s)-2-ethoxy-3-{4-[2-(10h-phenoxazin-10- yl)ethoxy]phenyl}propanoic acid / 1nyx
2-[(2,4-dichlorobenzoyl)amino]-5-(pyrimidin- 2-yloxy)benzoic acid / 1wm0
(2s)-(4-isopropylphenyl)[(2-methyl-3-oxo- 5,7-dipropyl-2,3-dihydro-1,2-benzisoxazol- 6-yl)oxy]acetate / 1zeo
2-{5-[3-(7-propyl-3-trifluoromethylbenzo[d]isoxazol- 6-yloxy)propoxy]indol-1-yl}ethanoic acid / 2ath
(5-{3-[(6-benzoyl-1-propyl-2-naphthyl)oxy]propoxy}- 1h-indol-1-yl)acetic acid / 2f4b
3-fluoro-n-[1-(4-fluorophenyl)-3-(2-thienyl)- 1h-pyrazol-5-yl]benzenesulfonamide / 2g0g
n-[1-(4-fluorophenyl)-3-(2-thienyl)-1h-pyrazol- 5-yl]-3,5-bis(trifluoromethyl)benzenesulfonamide / 2g0h
(2s)-3-(1-{[2-(2-chlorophenyl)-5-methyl-1,3- oxazol-4-yl]methyl}-1h-indol-5-yl)-2-ethoxypropanoic acid / 2gtk
[(1-{3-[(6-benzoyl-1-propyl-2-naphthyl)oxy]propyl}- 1h-indol-5-yl)oxy]acetic acid / 2hwq
2-[(1-{3-[(6-benzoyl-1-propyl-2-naphthyl)oxy]propyl}- 1h-indol-4-yl)oxy]-2-methylpropanoic acid / 2hwr

Conclusion: all ligands were docked correctly to the model prepared from 1fm9

PLA2

Ligand / pdb ID
6-phenyl-4(r)-(7-phenyl-heptanoylamino)-hexanoic acid / 1kqu
1-octadecyl-2-acetamido-2-deoxy-sn-glycerol- 3-phosphoethylmethyl sulfide / 1ayp
[3-(1-benzyl-3-carbamoylmethyl-2-methyl-1h- indol-5-yloxy)-propyl-]-phosphonic acid / 1db4
4-(1-benzyl-3-carbamoylmethyl-2-methyl-1h- indol-5-yloxy)-butyric acid / 1db5
1-benzyl-5-methoxy-2-methyl-1h-indol-3-yl)- acetic acid / 1dcy
(s)-5-(4-benzyloxy-phenyl)-4-(7-phenyl-heptanoylamino)- pentanoic acid / 1j1a
4-(s)-[(1-oxo-7-phenylheptyl)amino]-5-[4- (phenylmethyl)phenylthio]pentanoic acid / 1kvo
1-o-octyl-2-heptylphosphonyl-sn-glycero-3- phosphoethanolamine / 1poe

Conclusion: all ligands were docked correctly to the model prepared from 1kqu

PTP1B

Ligand / pdb ID
4-phosphonooxy-phenyl-methyl-[4-phosphonooxy]benzen / 1aax
4-carbamoyl-4-{[6-(difluoro-phosphono-methyl)- naphthalene-2-carbonyl]-amino}-butyric acid / 1bzc
6-(difluoro-phosphono-methyl)-naphthalene- 2-carboxylic acid / 1bzj
6-(oxalyl-amino)-1h-indole-5-carboxylic acid / 1c83
3-(oxalyl-amino)-naphthalene-2-carboxylic acid / 1c84
2-(oxalyl-amino)-benzoic acid / 1c85
2-(oxalyl-amino)-4,7-dihydro-5h-thieno[2,3- c]pyran-3-carboxylic acid / 1c87
2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid / 1c88
5-iodo-2-(oxalyl-amino)-benzoic acid / 1ecv
2-{4-[(2s)-2-[({[(1s)-1-carboxy-2-phenylethyl]amino}carbonyl)amino]- 3-oxo-3-(pentylamino)propyl]phenoxy}malonic acid / 1g7f
2-(carboxymethoxy)-5-[(2s)-2-({(2s)-2-[(3- carboxypropanoyl)amino] -3-phenylpropanoyl}amino)- 3-oxo-3-(pentylamino)propyl]benzoic acid / 1g7g
2-(oxalyl-amino)-4,7-dihydro-5h-thieno[2,3- c]thiopyran-3-carboxylic acid / 1gfy
5-(2-{2-[(tert-butoxy-hydroxy-methyl)-amino]- 1-hydroxy-3-phenyl-propylamino}-3-hydroxy- 3-pentylamino-propyl)-2-carboxymethoxy-benzoic acid / 1jf7
{[7-(difluoro-phosphono-methyl)-naphthalen- 2-yl]-difluoro-methyl}-phosphonic acid / 1kak
[(4-{4-[4-(difluoro-phosphono-methyl)-phenyl]- butyl}-phenyl)-difluoro-methyl]-phosphonic acid / 1kav

Conclusion: all ligands were docked correctly to the model prepared from 1c84