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diff --git a/plip/test/test_literature_validated.py b/plip/test/test_literature_validated.py new file mode 100644 index 0000000..f3f7cbc --- /dev/null +++ b/plip/test/test_literature_validated.py @@ -0,0 +1,754 @@ +# coding=utf-8 +""" +Protein-Ligand Interaction Profiler - Analyze and visualize protein-ligand interactions in PDB files. +test_literature_validated.py - Unit Tests for literature-validated cases. +""" + + +import unittest +from plip.structure.preparation import PDBComplex + + +class LiteratureValidatedTest(unittest.TestCase): + """Checks predictions against literature-validated interactions""" + + ############################################### + # Literature-validated cases from publication # + ############################################### + + 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_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_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_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_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_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_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_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_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_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_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)) + # 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_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_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_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_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_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_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_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_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 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_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 bridge to Trp176 + waterbridges = {wb.resnr for wb in s.water_bridges} + self.assertTrue({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_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 Thr59 + hbonds = {hbond.resnr for hbond in s.hbonds_pdon} + self.assertTrue({59}.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_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_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_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_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 bond to Ser237 + hbonds = {hbond.resnr for hbond in s.hbonds_pdon} + self.assertTrue({237}.issubset(hbonds)) + # pi-stacking interaction with Tyr157 + pistackres = {pistack.resnr for pistack in s.pistacking} + self.assertTrue({157}.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 + # res nr 52 mentioned in alternative conformation, not considered + hbonds = {hbond.resnr for hbond in s.hbonds_pdon} + self.assertTrue({137, 138}.issubset(hbonds)) + # Water bridges to Trp137 + # res nr 52 mentioned in alternative conformation not considered + waterbridges = {wb.resnr for wb in s.water_bridges} + self.assertTrue({322}.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_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_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)) + + ######################################### + # Additional literature-validated cases # + ######################################### + + 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)) + # #@todo Publication mentions additional possible hydrogen bond with Asp28B + # Hydrogen bonds with Asp-A25 are reported as a salt bridge as both partners have (potential) charges + + 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)) + # #@todo Paper describes additional hydrogen bond with Asp25A + + def test_3o7g(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_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)) |