def test_1HPX(self): """ HIV-1 Protease complexes with the inhibitor KNI-272 Reference: Structure of HIV-1 protease with KNI-272, a tight-binding transition-state analog containing allophenylnorstatine. Note that the residue numbering is different in the publication and the PDB structure. For residues in the B chain, the offset is -100 (e.g. Ile 50B in the PDB structure is Ile 150 in the paper). """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1hpx.pdb') bsid = 'KNI:B:900' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrophobic contacts to Val82, Ile84, Ile150 as part of flap (S1, S1' sites) hydroph = { str(hyd.resnr) + hyd.reschain for hyd in s.all_hydrophobic_contacts } self.assertTrue({'82A', '84A', '50B'}.issubset(hydroph)) # Hydrogen bonds hbonds = { str(hbond.resnr) + hbond.reschain for hbond in s.hbonds_ldon + s.hbonds_pdon } # Additional hbond to 25B not detected (low angle?) self.assertTrue({'29B', '48B', '27B', '25A'}.issubset(hbonds)) # Water bridges waterbridges = {str(wb.resnr) + wb.reschain for wb in s.water_bridges} # Waterbridge with Gly27 is detected instead of Ala28/Asp29 self.assertTrue({'50A', '50B', '29A'}.issubset(waterbridges)) print(waterbridges)
def test_ids(self): """Test if the atom IDs are correctly mapped from internal to original PDB.""" tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1vsn.pdb') bsid = 'NFT:A:283' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] for contact in s.hydrophobic_contacts: if contact.restype == 'ALA' and contact.resnr == 133: self.assertEqual(contact.ligatom_orig_idx, 1636) self.assertEqual(contact.bsatom_orig_idx, 994) if contact.restype == 'ASP' and contact.resnr == 61: self.assertEqual(contact.ligatom_orig_idx, 1639) self.assertEqual(contact.bsatom_orig_idx, 448) for contact in s.hbonds_ldon + s.hbonds_pdon: if contact.restype == 'GLN' and contact.resnr == 19: self.assertEqual(contact.a_orig_idx, 1649) self.assertEqual(contact.d_orig_idx, 153) if contact.restype == 'CYS' and contact.resnr == 25: self.assertEqual(contact.a_orig_idx, 1649) self.assertEqual(contact.d_orig_idx, 183) if contact.restype == 'ASN' and contact.resnr == 158: self.assertEqual(contact.d_orig_idx, 1629) self.assertEqual(contact.a_orig_idx, 1199) for contact in s.halogen_bonds: if contact.restype == 'TYR' and contact.resnr == 67: self.assertEqual(contact.don.x_orig_idx, 1627) self.assertEqual(contact.acc.o_orig_idx, 485) if contact.restype == 'LEU' and contact.resnr == 157: self.assertEqual(contact.don.x_orig_idx, 1628) self.assertEqual(contact.acc.o_orig_idx, 1191)
def test_2iuz(self): """Binding of C2-dicaffeine to Aspergilius fumigates(2iuz) Reference: Schüttelkopf et al. Screening-based discovery and structural dissection of a novel family 18 chitinase inhibitor.(2006) """ tmpmol = PDBComplex() tmpmol.load_pdb("./pdb/2iuz.pdb") bsid = "D1H:A:1440" for ligand in tmpmol.ligands: if ":".join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Trp137, Trp184 hbonds = { hbond.resnr for hbond in s.hbonds_pdon } # res nr 52 mentioned in alternative conformation, not considered self.assertTrue({137, 384}.issubset(hbonds)) # Water bridges to Trp137 waterbridges = { wb.resnr for wb in s.water_bridges } # res nr 52 mentioned in alternative conformation not considered self.assertTrue({137}.issubset(waterbridges)) # pi-stacking interaction with Trp384, Trp137 and Trp52 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({52, 137, 384}.issubset(pistackres))
def test_1HPX(self): """ HIV-1 Protease complexes with the inhibitor KNI-272 Reference: Structure of HIV-1 protease with KNI-272, a tight-binding transition-state analog containing allophenylnorstatine. Note that the residue numbering is different in the publication and the PDB structure. For residues in the B chain, the offset is -100 (e.g. Ile 50B in the PDB structure is Ile 150 in the paper). """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1hpx.pdb') bsid = 'KNI:B:900' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrophobic contacts to Val82, Ile84, Ile150 as part of flap (S1, S1' sites) hydroph = {str(hyd.resnr)+hyd.reschain for hyd in s.all_hydrophobic_contacts} self.assertTrue({'82A', '84A', '50B'}.issubset(hydroph)) # Hydrogen bonds hbonds = {str(hbond.resnr)+hbond.reschain for hbond in s.hbonds_ldon+s.hbonds_pdon} # Additional hbond to 25B not detected (low angle?) self.assertTrue({'29B', '48B', '27B', '25A'}.issubset(hbonds)) # Water bridges waterbridges = {str(wb.resnr)+wb.reschain for wb in s.water_bridges} # Waterbridge with Gly27 is detected instead of Ala28/Asp29 self.assertTrue({'50A', '50B', '29A'}.issubset(waterbridges)) print(waterbridges)
def test_1bma(self): """Binding of aminimide to porcine pancreatic elastase(1bma) Reference: Peisach et al. Interaction of a Peptidomimetic Aminimide Inhibitor with Elastase. (1995) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1bma.pdb') bsid = '0QH:A:256' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to val224 and Gln200 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({224, 200}.issubset(hbonds)) self.assertTrue({224, 200}.issubset(hbonds)) # hydrophobic interaction of Phe223 and val103 hydrophobics = { hydrophobic.resnr for hydrophobic in s.all_hydrophobic_contacts } self.assertTrue({223, 103}.issubset(hydrophobics)) # Water bridges to Ser203 not detected due to prioritization waterbridges = {wb.resnr for wb in s.water_bridges} self.assertTrue(set().issubset(waterbridges))
def test_3pxf(self): """Binding of ANS to CDK2 (3pxf) Reference: Betzi et al. Discovery of a potential allosteric ligand binding site in CDK2 (2012) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/3pxf.pdb') bsids = ['2AN:A:305', '2AN:A:304'] for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) in bsids: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsids[0]] # 2AN:A:305 # Hydrogen bonding of Asp145 and Phe146 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({145, 146}.issubset(hbonds)) # Salt bridge by Lys33 to sulfonate group saltb = {saltbridge.resnr for saltbridge in s.saltbridge_lneg} self.assertTrue({33}.issubset(saltb)) # Naphtalene positioned between Leu55 and Lys56, indicating hydrophobic interactions hydroph = {hydroph.resnr for hydroph in s.hydrophobic_contacts} self.assertTrue({55, 56}.issubset(hydroph)) s = tmpmol.interaction_sets[bsids[1]] # 2AN:A:304 # Salt bridges to sulfonate group by Lys56 and His71 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_lneg} self.assertTrue({56, 71}.issubset(saltb)) # Napthalene with hydrophobic interactions to Ile52 and Leu76 hydroph = {hydroph.resnr for hydroph in s.hydrophobic_contacts} self.assertTrue({52, 76}.issubset(hydroph))
def test_1bju(self): """Binding of ACPU to bovine tripsin(1bju) Reference: Presnell et al. Oxyanion-Mediated Inhibition of Serine Proteases.(1998) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1bju.pdb') bsid = 'GP6:A:910' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] #@todo Publication show hydrogen bond interactions for Gly219 # Hydrogen bonds to Ser190, Ser195, Gly219 and Asp189 hbonds = {hbond.resnr for hbond in s.hbonds_pdon+s.hbonds_ldon} self.assertTrue({189, 190, 195}.issubset(hbonds)) # Water bridges to Ser190 and Val227 # Water bridge to 190 not detected due to prioritization waterbridges = {wb.resnr for wb in s.water_bridges} self.assertTrue({227}.issubset(waterbridges)) # hydrophobic interaction of Leu99 hydrophobics = {hydrophobic.resnr for hydrophobic in s.all_hydrophobic_contacts} self.assertTrue({99}.issubset(hydrophobics)) # pi-stacking interaction with His57 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({57}.issubset(pistackres))
def test_1aku(self): """Binding of Flavin mononucleotido with D.Vulgaris(1aku) Reference: McCarthy et al. Crystallographic Investigation of the Role of Aspartate 95 in the Modulation of the Redox Potentials of DesulfoVibrio Vulgaris Flavodoxin.(2002) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1aku.pdb') bsid = 'FMN:A:150' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Tht59 and Trp60 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({59, 60}.issubset(hbonds)) # Water bridges to Asp63 and Tyr100 waterbridges = {wb.resnr for wb in s.water_bridges} # Water bridge to Tyr100 not detected due to prioritization self.assertTrue({63}.issubset(waterbridges)) # hydrophobic interaction of Trp60 hydrophobics = {hydrophobic.resnr for hydrophobic in s.all_hydrophobic_contacts} self.assertTrue({60}.issubset(hydrophobics)) # pi-stacking interaction with Tyr98 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({98}.issubset(pistackres))
def test_1hvi(self): """HIV-1 protease in complex with Diol inhibitor (1hvi) Reference: Influence of Stereochemistry on Activity and Binding Modes for C2 Symmetry-Based Diol Inhibitors of HIV-1 Protease (1994) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1hvi.pdb') bsid = 'A77:A:800' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Water bridges waterbridges = {str(wb.resnr) + wb.reschain for wb in s.water_bridges} # #@todo Water bridge with 50B not detected self.assertTrue({ '50A' }.issubset(waterbridges)) # Bridging Ile-B50 and Ile-A50 with ligand # pi-cation Interactions picat = {pication.resnr for pication in s.pication_laro} self.assertEqual( {8}, picat) # Described as weakly polar contact/stacking in paper # Hydrogen bonds hbonds = { str(hbond.resnr) + hbond.reschain for hbond in s.hbonds_pdon + s.hbonds_ldon } self.assertTrue({'25B', '27A', '27B', '48A', '48B'}.issubset(hbonds))
def test_2w0s(self): """Binding of Vacc-TK to TDP (2w0s) Reference: Caillat et al. Crystal structure of poxvirus thymidylate kinase: An unexpected dimerization has implications for antiviral therapy (2008) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/2w0s.pdb') bsid = 'BVP:B:1207' # Complex of BVDU with Magnesium Cofactor for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonding of Tyr101 and Arg72 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({101, 72}.issubset(hbonds)) # Halogen Bonding of Asn65 halogens = {halogen.resnr for halogen in s.halogen_bonds} self.assertTrue({65}.issubset(halogens)) # pi-stacking interaction with Phe68 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({68}.issubset(pistackres)) # Saltbridge to Arg41 and Arg93 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_lneg} self.assertTrue({41, 93}.issubset(saltb))
def test_4kya(self): """Binding of non-classical TS inhibitor 3 with Toxoplasma gondii TS-DHFR(4kya) Reference: Zaware et al. Structural basis of HIV-1 capsid recognition by PF74 and CPSF6(2014) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/4kya.pdb') bsid = '1UG:E:702' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Ala609 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({609}.issubset(hbonds)) # Saltbridge to Asp513 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_pneg} self.assertTrue({513}.issubset(saltb)) # hydrophobic interaction of Ile402, Leu516, Phe520 and Met608 hydrophobics = { hydrophobic.resnr for hydrophobic in s.all_hydrophobic_contacts } self.assertTrue({402, 516, 520, 608}.issubset(hydrophobics)) # pi-stacking interaction with Trp403 and Phe520 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({403, 520}.issubset(pistackres))
def test_2iuz(self): """Binding of C2-dicaffeine to Aspergilius fumigates(2iuz) Reference: Schüttelkopf et al. Screening-based discovery and structural dissection of a novel family 18 chitinase inhibitor.(2006) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/2iuz.pdb') bsid = 'D1H:A:1440' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Trp137, Trp184 hbonds = { hbond.resnr for hbond in s.hbonds_pdon } # res nr 52 mentioned in alternative conformation, not considered self.assertTrue({137, 384}.issubset(hbonds)) # Water bridges to Trp137 waterbridges = { wb.resnr for wb in s.water_bridges } # res nr 52 mentioned in alternative conformation not considered self.assertTrue({137}.issubset(waterbridges)) # pi-stacking interaction with Trp384, Trp137 and Trp52 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({52, 137, 384}.issubset(pistackres))
def test_3r0t(self): """Binding of protein kinase CK2 alpha subunit in with the inhibitor CX-5279 (3r0t) Reference: Battistutta et al. Unprecedented selectivity and structural determinants of a new class of protein kinase CK2 inhibitors in clinical trials for the treatment of cancer (2011). """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/3r0t.pdb') bsid = 'FU9:A:338' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Val116 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({116}.issubset(hbonds)) # Water bridges to Lys68 and Trp176 waterbridges = {wb.resnr for wb in s.water_bridges} self.assertTrue({68, 176}.issubset(waterbridges)) # Saltbridge to Ly68 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_lneg} self.assertTrue({68}.issubset(saltb)) # hydrophobic interaction of Val66, Phe113 and Ile174 hydrophobics = {hydrophobic.resnr for hydrophobic in s.all_hydrophobic_contacts} self.assertTrue({66, 113, 174}.issubset(hydrophobics)) # pi-stacking interaction with His160 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({160}.issubset(pistackres))
def test_1n7g(self): """Binding of NADPH to MURI from Arabidopsis thaliana (1n7g) Reference: Mulichak et al. Structure of the MUR1 GDP-mannose 4, 6-dehydratase from Arabidopsis thaliana: implications for ligand binding and specificity(2002) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1n7g.pdb') bsid = 'NDP:A:701' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Thr37, Gly38, Gln39, Asp40, Arg60, Leu92, Asp91, Ser63, Leu92, Ala115, Ser117, # Tyr128, Tyr185, Lys189, His215 and Arg220 # Publication give the Prediction for Asp91 as hydrogen bond, when this contains two acceptor atoms. hbonds = {hbond.resnr for hbond in s.hbonds_pdon} # #@todo Hbond to 128 not detected self.assertTrue({37, 38, 39, 40, 92, 63, 92, 115, 117, 185, 189, 215, 220}.issubset(hbonds)) # Water bridges to Gly35, Thr37, Gly38, Asp40, Arg60, Arg61, Ser63, Asn66, Ser117, Tyr128, Lys189, Arg220 waterbridges = {wb.resnr for wb in s.water_bridges} # Hydrogen bonds to 35, 37, 38, 40, 63, 117, 128, 189, 220 not detected due to prioritization self.assertTrue({60, 66, 61}.issubset(waterbridges)) # Saltbridge to arg60, Arg61, Arg69 and Arg220 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_lneg} # #@todo Additional saltbridges report to 69 and 200 (with large distances) self.assertTrue({60, 61}.issubset(saltb)) # Cation-pi interactions with Arg60 picat = {pication.resnr for pication in s.pication_laro} self.assertEqual({60}, picat)
def test_3shy(self): """Binding of 5FO to PDE5A1 catalytic domain(3shy) Reference: Xu et al. Utilization of halogen bond in lead optimization: A case study of rational design of potent phosphodiesterase type 5 (PDE5) inhibitors.(2011) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/3shy.pdb') bsid = '5FO:A:1' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Gln817 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({817}.issubset(hbonds)) # hydrophobic interaction of Tyr612 hydrophobics = { hydrophobic.resnr for hydrophobic in s.all_hydrophobic_contacts } self.assertTrue({612}.issubset(hydrophobics)) # pi-stacking interaction with Phe820 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({820}.issubset(pistackres)) # Halogen Bonding of Tyr612 halogens = {halogen.resnr for halogen in s.halogen_bonds} self.assertTrue({612}.issubset(halogens))
def test_3r0t(self): """Binding of protein kinase CK2 alpha subunit in with the inhibitor CX-5279 (3r0t) Reference: Battistutta et al. Unprecedented selectivity and structural determinants of a new class of protein kinase CK2 inhibitors in clinical trials for the treatment of cancer..(2011) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/3r0t.pdb') bsid = 'FU9:A:338' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Val116 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({116}.issubset(hbonds)) # Water bridges to Lys68 and Trp176 waterbridges = {wb.resnr for wb in s.water_bridges} self.assertTrue({68, 176}.issubset(waterbridges)) # Saltbridge to Ly68 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_lneg} self.assertTrue({68}.issubset(saltb)) # hydrophobic interaction of Val66, Phe113 and Ile174 hydrophobics = {hydrophobic.resnr for hydrophobic in s.all_hydrophobic_contacts} self.assertTrue({66, 113, 174}.issubset(hydrophobics)) # pi-stacking interaction with His160 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({160}.issubset(pistackres))
def test_4rao(self): """Binding of (4rao) Reference: Keough et al. Aza-acyclic Nucleoside Phosphonates Containing a Second Phosphonate Group As Inhibitors of the Human, Plasmodium falciparum and vivax 6‑Oxopurine Phosphoribosyltransferases and Their Prodrugs As Antimalarial Agents (2004) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/4rao.pdb') bsid = '3L7:B:301' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Val187, Lys165, Thr141, Lys140, Gly139, Thr138, Asp137 hbonds = {hbond.resnr for hbond in s.hbonds_pdon } # res nr 100, 68, 69 and 199 in alternative conformation, self.assertTrue({137, 138, 139, 140, 141, 165, 187}.issubset(hbonds)) # Water bridges to Asp137, Thr141, Met142, Arg199 and Gly139 # res nr 199 and 142 in alternative conformation # Water bridges to 137m 141, 139 not detected due to prioritization # pi-stacking interaction with Phe186 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({186}.issubset(pistackres))
def test_4rdl(self): """Binding of Norovirus Boxer P domain with Lewis y tetrasaccharide(4rdl) Reference: Hao et al. Crystal structures of GI.8 Boxer virus P dimers in complex with HBGAs, a novel evolutionary path selected by the Lewis epitope..(2014) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/4rdl.pdb') bsid = 'FUC:A:601' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[ bsid] # Instead of FUC-A-604 (sugar representative) # Water bridges to Asn395 waterbridges = {wb.resnr for wb in s.water_bridges} self.assertTrue({395}.issubset(waterbridges)) # Hydrogen bonds to Thr347, Gly348 and Asn395 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({347, 348, 395}.issubset(hbonds)) # hydrophobic interaction of Trp392 hydrophobics = { hydrophobic.resnr for hydrophobic in s.all_hydrophobic_contacts } self.assertTrue({392}.issubset(hydrophobics))
def test_1p5e(self): """Binding of TBS to CDK2(1p5e) Reference: De Moliner et al. Alternative binding modes of an inhibitor to two different kinases. (2003) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1p5e.pdb') bsid = 'TBS:A:301' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Halogen Bonding of Ile10 and Leu83 halogens = {halogen.resnr for halogen in s.halogen_bonds} self.assertTrue({10, 83}.issubset(halogens))
def test_1vsn(self): """Binding of NFT to Cathepsin K (1vsn) Reference: Li et al. Identification of a potent and selective non-basic cathepsin K inhibitor. (2006) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1vsn.pdb') bsid = 'NFT:A:283' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonding to Gly66 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({66}.issubset(hbonds))
def test_3OG7(self): """Inhibitor PLX4032 binding to B-RAF(V600E) (3og7) Reference: Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma (2010) """ tmpmol = PDBComplex() tmpmol.load_pdb("./pdb/3og7.pdb") bsid = "032:A:1" for ligand in tmpmol.ligands: if ":".join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds hbonds = {str(hbond.resnr) + hbond.reschain for hbond in s.hbonds_pdon + s.hbonds_ldon} self.assertTrue({"594A", "530A"}.issubset(hbonds))
def test_1acj(self): """Binding of Tacrine (THA) to active-site gorge of acetylcholinesterase (1acj) Reference: Harel et al. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase.. (1993) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1acj.pdb') bsid = 'THA:A:999' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # pi-stacking interaction with Phe330 and Trp84 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({330, 84}.issubset(pistackres))
def test_2pvb(self): """Pike parvalbumin binding calcium (2pvb) Reference: Harding. The architecture of metal coordination groups in proteins. (2004), Fig. 6 """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/2pvb.pdb') bsid = 'CA:A:110' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Ca atom with square pyramidal geometry (coordination number 5) self.assertEqual(s.metal_complexes[0].coordination_num, 5) self.assertEqual(s.metal_complexes[0].geometry, 'square.pyramidal')
def test_3OG7(self): """Inhibitor PLX4032 binding to B-RAF(V600E) (3og7) Reference: Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma (2010) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/3og7.pdb') bsid = '032:A:1' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds hbonds = {str(hbond.resnr)+hbond.reschain for hbond in s.hbonds_pdon+s.hbonds_ldon} self.assertTrue({'594A', '530A'}.issubset(hbonds))
def test_1osn(self): """Binding of VZV-tk to BVDU-MP (2reg) Reference: Bird et al. Crystal structures of Varicella Zoster Virus Thyrimidine Kinase. (2003) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1osn.pdb') bsid = 'BVP:A:500' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Sandwiched pi-stacking involving Phe93 and Phe139 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({93, 139}.issubset(pistackres)) # Hydrogen bonding of Gln90 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({90}.issubset(hbonds))
def test_4qnb(self): """Binding of (4qnb) Reference: Bhattacharya et al. Structural basis of HIV-1 capsid recognition by PF74 and CPSF6(2014) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/4qnb.pdb') bsid = '1B0:A:301' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Asn57 and Lys70 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({57, 70}.issubset(hbonds)) # Cation-pi interactions with Lys70 picat = {pication.resnr for pication in s.pication_laro} self.assertEqual({70}, picat)
def test_4alw(self): """Binding of benzofuropyrimidinones compound 3 to PIM-1 (4alw) Reference: Tsuhako et al. The design, synthesis, and biological evaluation of PIM kinase inhibitors.(2012) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/4alw.pdb') bsid = 'HY7:A:1308' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Asp186 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({186}.issubset(hbonds)) # Saltbridge to A186 and Glu171 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_pneg} self.assertTrue({186, 171}.issubset(saltb))
def test_1eve(self): """Binding of anti-Alzheimer drug E2020 to acetylcholinesterase from Torpedo californica (1eve) Reference: Chakrabarti et al. Geometry of nonbonded interactions involving planar groups in proteins. (2007) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1eve.pdb') bsid = 'E20:A:2001' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Aromatic stacking with Trp84 and Trp279 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({84, 279}.issubset(pistackres)) # Pi-Cation interaction of Phe330 with ligand pication = {pication.resnr for pication in s.pication_paro} self.assertTrue({330}.issubset(pication))
def test_3thy(self): """Binding of ADP tp MutS(3thy) Reference: Shikha et al. Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops.(2012) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/3thy.pdb') bsid = 'ADP:A:935' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Saltbridge to His295 and Lys675 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_lneg} self.assertTrue({675}.issubset(saltb)) # pi-stacking interaction with Tyr815 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({815}.issubset(pistackres))
def process_pdb(pdbfile, outpath, as_string=False, outputprefix='report'): """Analysis of a single PDB file. Can generate textual reports XML, PyMOL session files and images as output.""" if not as_string: startmessage = '\nStarting analysis of %s\n' % pdbfile.split('/')[-1] else: startmessage = "Starting analysis from stdin.\n" write_message(startmessage) write_message('='*len(startmessage)+'\n') mol = PDBComplex() mol.output_path = outpath mol.load_pdb(pdbfile, as_string=as_string) # #@todo Offers possibility for filter function from command line (by ligand chain, position, hetid) for ligand in mol.ligands: mol.characterize_complex(ligand) create_folder_if_not_exists(outpath) # Generate the report files streport = StructureReport(mol, outputprefix=outputprefix) config.MAXTHREADS = min(config.MAXTHREADS, len(mol.interaction_sets)) ###################################### # PyMOL Visualization (parallelized) # ###################################### if config.PYMOL or config.PICS: try: from plip.modules.visualize import visualize_in_pymol except ImportError: from modules.visualize import visualize_in_pymol complexes = [VisualizerData(mol, site) for site in sorted(mol.interaction_sets) if not len(mol.interaction_sets[site].interacting_res) == 0] if config.MAXTHREADS > 1: write_message('\nGenerating visualizations in parallel on %i cores ...' % config.MAXTHREADS) parfn = parallel_fn(visualize_in_pymol) parfn(complexes, processes=config.MAXTHREADS) else: [visualize_in_pymol(plcomplex) for plcomplex in complexes] if config.XML: # Generate report in xml format streport.write_xml(as_string=config.STDOUT) if config.TXT: # Generate report in txt (rst) format streport.write_txt(as_string=config.STDOUT)
def test_3tah(self): """Binding of BGO to an an N11A mutant of the G-protein domain of FeoB.(3tah) Reference: Ash et al. The structure of an N11A mutant of the G-protein domain of FeoB.(2011) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/3tah.pdb') bsid = 'BGO:A:300' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Ala11, Lys14, Thr15, Ser16, Asp113, Met114, Ala143 and Asp113 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({11, 13, 14, 15, 16, 113, 114, 143, 113}.issubset(hbonds)) # Water bridges to Ala11 not detected due to prioritization of hydrogen bonds # Saltbridge to Asp116 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_pneg} self.assertTrue({116}.issubset(saltb))
def test_1hii(self): """HIV-2 protease in complex with novel inhibitor CGP 53820 (1hii) Reference: Comparative analysis of the X-ray structures of HIV-1 and HIV-2 proteases in complex with CGP 53820, a novel pseudosymmetric inhibitor (1995) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1hii.pdb') bsid = 'C20:B:101' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Water bridges waterbridges = {str(wb.resnr)+wb.reschain for wb in s.water_bridges} self.assertTrue({'50A', '50B'}.issubset(waterbridges)) # Bridging Ile-B50 and Ile-A50 with ligand # Hydrogen bonds hbonds = {str(hbond.resnr)+hbond.reschain for hbond in s.hbonds_pdon+s.hbonds_ldon} self.assertTrue({'27A', '27B', '29A', '48A', '48B'}.issubset(hbonds))
def test_4pjt(self): """Binding of BMN 673 to catPARP1(4pj7) Reference: Aoyagi-Scharber et al. Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from dihydropyridophthalazinone.(2014) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/4pjt.pdb') bsid = '2YQ:D:1104' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Gly863 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({863}.issubset(hbonds)) # pi-stacking interaction with Tyr889 and Tyr907 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({889, 907}.issubset(pistackres))
def test_2efj(self): """Binding of teobromine to 1,7 dimethylxanthine methyltransferase(2efj) Reference: McCarthy et al. The Structure of Two N-Methyltransferases from the Caffeine Biosynthetic Pathway.(2007) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/2efj.pdb') bsid = '37T:A:502' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Trp161, Ser237 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({161, 237}.issubset(hbonds)) # pi-stacking interaction with Tyr157 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({157}.issubset(pistackres))
def test_1vfy(self): """Phosphatidylinositol-3-phosphate binding FYVE domain of VPS27P protein (1vfy) Reference: Harding. The architecture of metal coordination groups in proteins. (2004), Fig. 5 """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1vfy.pdb') bsid = 'ZN:A:300' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Coordination by four cysteines metalres = [mres.restype for mres in s.metal_complexes] self.assertEqual(set(metalres), {'CYS'}) # Zn atom with tetrahedral geometry (coordination number 4) self.assertEqual(s.metal_complexes[0].coordination_num, 4) self.assertEqual(s.metal_complexes[0].geometry, 'tetrahedral')
def test_1het(self): """Liver alcohol deshydrogenase (1het) Reference: Harding. The architecture of metal coordination groups in proteins. (2004), Fig. 2 """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1het.pdb') bsid = 'ZN:A:401' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Coordination by four cysteines metalres = [mres.restype + str(mres.resnr) for mres in s.metal_complexes] self.assertEqual(set(metalres), {'CYS97', 'CYS100', 'CYS103', 'CYS111'}) # Zn atom with tetrahedral geometry (coordination number 4) self.assertEqual(s.metal_complexes[0].coordination_num, 4) self.assertEqual(s.metal_complexes[0].geometry, 'tetrahedral')
def test_2reg(self): """Binding of choline to ChoX (2reg) Reference: Oswald et al. Crystal structures of the choline/acetylcholine substrate-binding protein ChoX from Sinorhizobium meliloti in the liganded and unliganded-closed states. (2008) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/2reg.pdb') bsid = 'CHT:A:1' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Cation-pi interactions with Trp43, Trp90, Trp205, and Tyr119 picat = {pication.resnr for pication in s.pication_paro} self.assertEqual({43, 90, 205, 119}, picat) # Saltbridge to Asp45 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_pneg} self.assertEqual({45}, saltb)
def test_2q8q(self): """Crystal Structure of S. aureus IsdE complexed with heme (2q8q) Reference: Grigg et al. Heme coordination by Staphylococcus aureus IsdE. (2007) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/2q8q.pdb') bsid = 'HEM:A:300' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Coordination by four nitrogens of heme itself and one additional histidine from the protein metalres = [mres.restype for mres in s.metal_complexes] self.assertEqual(metalres.count('HEM'), 4) self.assertEqual(metalres.count('HIS'), 1) # Fe atom with square pyramidal geometry (coordination number 5) self.assertEqual(s.metal_complexes[0].coordination_num, 5) self.assertEqual(s.metal_complexes[0].geometry, 'square.pyramidal')
def test_3o1h(self): """Binding of TMAO to TorT-TorS system(3o1h) Reference: Hendrickson et al. An Asymmetry-to-Symmetry Switch in Signal Transmission by the Histidine Kinase Receptor for TMAO.(2013) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/3o1h.pdb') bsid = 'TMO:B:1' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Hydrogen bonds to Trp45 hbonds = {hbond.resnr for hbond in s.hbonds_ldon} self.assertTrue({45}.issubset(hbonds)) # Water bridges to Trp45 not detected due to priorization of hydrogen bonds # Cation-pi interactions with Tyr44 picat = {pication.resnr for pication in s.pication_paro} self.assertEqual({44}, picat)
def test_2zoz(self): """Binding of CgmR to ethidium(2z0z) Reference: Itou et al. Crystal Structures of the Multidrug Binding Repressor Corynebacterium glutamicum CgmR in Complex with Inducers and with an Operator. (2010) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/2zoz.pdb') bsid = 'ET:B:184' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # pi-stacking interaction with Trp63 and Phe147 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({147}.issubset(pistackres)) # Trp 63!! # hydrophobic interaction of Leu59, Leu88, Trp63, Trp113, Phe147 hydrophobics = {hydrophobic.resnr for hydrophobic in s.all_hydrophobic_contacts} self.assertTrue({59, 88, 63, 113, 147}.issubset(hydrophobics)) self.assertTrue({59, 88, 63, 92, 113, 147}.issubset(hydrophobics))
def test_1rmd(self): """Zinc binding sites in RAG1 dimerization domain (1rmd) Reference: Harding. The architecture of metal coordination groups in proteins. (2004), Fig. 1a """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1rmd.pdb') bsid = 'ZN:A:119' for ligand in tmpmol.ligands: if ':'.join([ligand.hetid, ligand.chain, str(ligand.position)]) == bsid: tmpmol.characterize_complex(ligand) s = tmpmol.interaction_sets[bsid] # Coordination by three cysteines and one histidine of the protein metalres = [mres.restype for mres in s.metal_complexes] self.assertEqual(metalres.count('CYS'), 3) self.assertEqual(metalres.count('HIS'), 1) # Zn atom with tetrahedral geometry (coordination number 4) self.assertEqual(s.metal_complexes[0].coordination_num, 4) self.assertEqual(s.metal_complexes[0].geometry, 'tetrahedral')