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
