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diff --git a/plip/test/test_literature_validated.py b/plip/test/test_literature_validated.py deleted file mode 100644 index f3f7cbc..0000000 --- a/plip/test/test_literature_validated.py +++ /dev/null @@ -1,754 +0,0 @@ -# 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)) |