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_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_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_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') s = tmpmol.interaction_sets['NDP-A-701'] # 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_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_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_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_dna_rna(self): """Test if DNA and RNA is correctly processed as ligands""" tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1tf6.pdb') # DNA ligand four times consisting of 31 parts (composite) self.assertEqual([len(ligand.members) for ligand in tmpmol.ligands].count(31), 4) for ligset in [set((x[0] for x in ligand.members)) for ligand in tmpmol.ligands]: if len(ligset) == 4: # DNA only contains four bases self.assertEqual(ligset, set(['DG', 'DC', 'DA', 'DT']))
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') s = tmpmol.interaction_sets['NFT-A-283'] # Hydrogen bonding to Gly66 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({66}.issubset(hbonds))
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') s = tmpmol.interaction_sets['TBS-A-301'] # Halogen Bonding of Ile10 and Leu83 halogens = {halogen.resnr for halogen in s.halogen_bonds} self.assertTrue({10, 83}.issubset(halogens))
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') s = tmpmol.interaction_sets['032-A-1'] # 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') s = tmpmol.interaction_sets['THA-A-999'] # pi-stacking interaction with Phe330 and Trp84 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({330, 84}.issubset(pistackres))
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') s = tmpmol.interaction_sets['E20-A-2001'] # 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_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') s = tmpmol.interaction_sets['HY7-A-1308'] # 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_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') s = tmpmol.interaction_sets['1B0-A-301'] # 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_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') s = tmpmol.interaction_sets['ADP-A-935'] # 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 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') s = tmpmol.interaction_sets['BVP-A-500'] # 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_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_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') s = tmpmol.interaction_sets['2YQ-D-1104'] # 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') s = tmpmol.interaction_sets['37T-A-502'] # 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_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') s = tmpmol.interaction_sets['CHT-A-1'] # 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_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') s = tmpmol.interaction_sets['C20-B-101'] # 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_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_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') s = tmpmol.interaction_sets['BGO-A-300'] # 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_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') s = tmpmol.interaction_sets['TMO-B-1'] # Hydrogen bonds to Trp45 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} 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_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_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_1h2t(self): """Binding of methylated guanosine to heterodimeric nuclear-cap binding complex (1h2t) Reference: Chakrabarti et al. Geometry of nonbonded interactions involving planar groups in proteins. (2007) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1h2t.pdb') s = tmpmol.interaction_sets['7MG-Z-1152'] # Sandwiched pi-stacking involving Tyr20 and Tyr43 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({20, 43}.issubset(pistackres)) # Hydrogen bond with R112 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({112}.issubset(hbonds)) # Salt bridge with D116 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_pneg} self.assertTrue({116}.issubset(saltb))
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 } # Additional hydrogen bond to residue 530A reported self.assertTrue({'594A'}.issubset(hbonds))
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_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_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')
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_1ay8(self): """Binding of PLP to aromatic amino acid aminotransferase(1ay8) Reference: Okamoto et al. Crystal structures of Paracoccus denitrificans aromatic amino acid aminotransferase: a substrate recognition site constructed by rearrangement of hydrogen bond network..(1998) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1ay8.pdb') bsid = 'PLP:A:413' 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 Gly108, Thr109, Asn194 and Ser257 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({108, 109, 194, 257}.issubset(hbonds)) # Saltbridge to Ly258 and Arg266 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_lneg} self.assertTrue({258, 266}.issubset(saltb)) # pi-stacking interaction with Trp140 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({140}.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_1h2t(self): """Binding of methylated guanosine to heterodimeric nuclear-cap binding complex (1h2t) Reference: Chakrabarti et al. Geometry of nonbonded interactions involving planar groups in proteins. (2007) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1h2t.pdb') bsid = 'GDP:Z:1151' 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 Tyr20 and Tyr43 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({20, 43}.issubset(pistackres)) # Hydrogen bond with R112 hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({112}.issubset(hbonds)) # Salt bridge with D116 saltb = {saltbridge.resnr for saltbridge in s.saltbridge_pneg} self.assertTrue({116}.issubset(saltb))
def test_1rla(self): """Rat liver arginase, a binuclear manganese metalloenzyme (1rmd) Reference: Harding. The architecture of metal coordination groups in proteins. (2004), Fig. 1b """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1rla.pdb') bsid = 'MN: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] # Coordination by one histidine, three aspartic acid residues, and one water molecule metalres = [mres.restype for mres in s.metal_complexes] self.assertEqual(metalres.count('HIS'), 1) self.assertEqual(metalres.count('ASP'), 3) self.assertEqual(metalres.count('HOH'), 1) # Mn 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_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_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_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_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_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_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_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_1xdn(self): """Binding of ATP to RNA editing ligase 1 (1xdn) Reference: Deng et al. High resolution crystal structure of a key editosome enzyme from Trypanosoma brucei: RNA editing ligase 1. (2004) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/1xdn.pdb') bsid = 'ATP:A:501' 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 Arg111, Ile61 (backbone), Asn92, Val88, Lys87 and Glu86# hbonds = {hbond.resnr for hbond in s.hbonds_pdon} self.assertTrue({111, 61, 92, 88, 87}.issubset(hbonds)) #@todo Publication shows additional waterbridge interacction for Ile59, Glu159 # Water bridges to Lys307, Arg309 and 111 from phosphate groups waterbridges = {wb.resnr for wb in s.water_bridges} # Water bridge to 60 not found due to prioritization self.assertTrue({307, 309, 111}.issubset(waterbridges)) # pi-stacking interaction with Phe209 pistackres = {pistack.resnr for pistack in s.pistacking} self.assertTrue({209}.issubset(pistackres))
def test_4agl(self): """Binding of P53 to PhiKan784(4agl) Reference: Wilcken et al. Halogen-Enriched Fragment Libraries as Leads for Drug Rescue of Mutant p53.(2012) """ tmpmol = PDBComplex() tmpmol.load_pdb('./pdb/4agl.pdb') bsid = 'P84:A:400' 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 to Val147 waterbridges = {wb.resnr for wb in s.water_bridges} self.assertTrue({147}.issubset(waterbridges)) # hydrophobic interaction of Thr150 hydrophobics = { hydrophobic.resnr for hydrophobic in s.all_hydrophobic_contacts } self.assertTrue({150}.issubset(hydrophobics)) # Halogen Bonding of Leu145 halogens = {halogen.resnr for halogen in s.halogen_bonds} self.assertTrue({145}.issubset(halogens))
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_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_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 run_plip(pdb, pdb_filepath, dump=True, dumpdir='', resdf=False, max_res_count=4000): # input: one pdb index, (list of sequences to check - maybe process from all data later) # main: load pdb from path # out: status of job, save results in file during function run # out-format: dict of ligands: keys are ligands ids (name:chain:resnum) and values - # lists of dicts, each dict one interaction # out-format-alt: dataframe for pdb with ligands as rows and columns: # restype_l, reschain_l, resnr_l, inter_type, restype, reschain, resnr, inter_data(maybe without already present columns) if dumpdir != '' and dump: assert dumpdir[-1] == '/', "dumpdir must end with '/'" picklename = dumpdir + pdb + '.p' if dump: if os.path.isfile(picklename): print('=> ' + pdb + ': in cache') if resdf: return pd.read_pickle(picklename) else: return True # unzip if pdb is gzipped if pdb_filepath[-3:] == '.gz': try: pdb_filepath = get_unzipped_tempfile(pdb_filepath) except FileNotFoundError: print('=> ' + pdb + ': Gz file not found') return False gz = True else: gz = False # first try to parse the structure with Bio.PDB #parser = PDBParser(PERMISSIVE=0) #try: #structure = parser.get_structure('temp', pdb_filepath) #except PDBConstructionException: # print('=> ' + pdb + ': Problem with parsing') # return False # check the number of residues #res_count = sum([len(list(model.get_residues())) for model in structure]) #if res_count>=max_res_count: # print('=> ' + pdb + ': The input molecule is too big (%d residues)' % res_count) # return False ligand_interactions = [] # PLIP analysis mol = PDBComplex() try: mol.load_pdb(pdb_filepath) except: print('=> ' + pdb + ': File not found') return False ligand_list_from_mol = [x.hetid for x in mol.ligands] print('=> ' + pdb + ': ' + str(len(ligand_list_from_mol)) + ' ligands to process') if ligand_list_from_mol == 0: return False try: mol.analyze() except TypeError: print('=> ' + pdb + ': Problem with parsing') return False for bsid in [ ":".join([x.hetid, x.chain, str(x.position)]) for x in mol.ligands ]: # for every ligand encountered in pdb interactions = mol.interaction_sets[ bsid] # Contains all interaction data for inter in interactions.all_itypes: inter_parsed = plip_parse.parse_inter(inter) ligand_interactions.append( convert_interaction_for_df(pdb, inter_parsed)) # create df for pdb df = pd.DataFrame(ligand_interactions, columns=[ 'pdb', 'restype_l', 'reschain_l', 'resnr_l', 'inter_type', 'restype', 'reschain', 'resnr', 'inter_data' ]) if dump: pickle.dump(df, open(picklename, 'wb')) # dump df if gz: # del tempfile os.remove(pdb_filepath) if resdf: return df else: return True
class Analyze: def __init__(self, protein, ligand, within=7.5): self.protein = protein self.ligand = ligand genASite = GenActiveSite(within=within) self.asite = genASite(self.protein, self.ligand) renumberResidues(self.asite) log(f'nAtoms of asite {self.asite.GetNumAtoms()}') complex = Chem.CombineMols(self.asite, self.ligand) self.pmol = PDBComplex() cont = Chem.MolToPDBBlock(complex).replace('UNL 1', 'MOL 1') self.pmol.load_pdb(cont, as_string=True) self.pmol.analyze() def getPLIPComplexToProteinMap(self): N = self.protein.GetNumAtoms() protein_coords = getCoordinates(self.protein) cpmap = {} for i in self.pmol.atoms: atom = self.pmol.get_atom(i) d = np.linalg.norm(np.tile(np.array(atom.coords), N).reshape( (N, 3)) - protein_coords, axis=1) minidx = d.argmin() if d[minidx] < 1e-3: cpmap[atom.idx] = minidx.item() return cpmap def getPLIPComplexToLigandMap(self): N = self.ligand.GetNumAtoms() ligand_coords = getCoordinates(self.ligand) clmap = {} for i in self.pmol.atoms: atom = self.pmol.get_atom(i) d = np.linalg.norm(np.tile(np.array(atom.coords), N).reshape( (N, 3)) - ligand_coords, axis=1) minidx = d.argmin() if d[minidx] < 1e-3: clmap[atom.idx] = minidx.item() return clmap def getPLIPComplexToASiteMap(self): N = self.asite.GetNumAtoms() asite_coords = getCoordinates(self.asite) camap = {} for i in self.pmol.atoms: atom = self.pmol.get_atom(i) d = np.linalg.norm(np.tile(np.array(atom.coords), N).reshape( (N, 3)) - asite_coords, axis=1) minidx = d.argmin() if d[minidx] < 1e-3: camap[atom.idx] = minidx.item() return camap def interactions(self): camap = self.getPLIPComplexToASiteMap() clmap = self.getPLIPComplexToLigandMap() for bsite, iacts in self.pmol.interaction_sets.items(): for ia in iacts.all_itypes: iact = Inter(ia) if not iact.isValid(): continue aidxs = list(map(lambda x: camap[x], iact.P())) lidxs = list(map(lambda x: clmap[x], iact.L())) yield bsite, iact.name, aidxs, lidxs
def analyze_with_plip(pdb): pdbcomplex = PDBComplex() pdbcomplex.load_pdb(pdb, as_string=True) pdbcomplex.analyze() pdbcomplex.sourcefiles['filename'] = '/dev/null' return pdbcomplex