title: Interaction of human chymase with ginkgolides, terpene trilactones of Ginkgo biloba investigated by molecular docking simulations.
abstract: The search for natural chymase inhibitors has a good potential to provide a novel therapeutic approach against the cardiovascular diseases and other heart ailments. We selected from literature 20 promising Ginkgo biloba compounds, and tested them for their potential ability to bind chymase enzyme using docking and a deep analysis of surface pocket features. Docking results indicated that the compounds may interact with the active site of human chymase, with favorable distinct interactions with important residues Lys40, His57, Lys192, Phe191, Val146, Ser218, Gly216, and Ser195. In particular, proanthocyanidin is the one with the best-predicted binding energy, with seven hydrogen bonds. Interestingly, all active G. biloba compounds have formed the hydrogen bond interactions with the positively charged Lys192 residue at the active site, involved in the mechanism of pH enhancement for the cleavage of angiotensin I site. Ginkgolic acid and proanthocyanidin have better predicted binding energy towards chymase than other serine proteases, i.e kallikrein, tryptase and elastase, suggesting specificity for chymase inhibition. Our study suggests these G. biloba compounds are a promising starting point for developing chymase inhibitors for the potential development of future drugs.
authors.affiliation: Istituto di Scienze dell'Alimentazione - CNR, Via Roma 64, Avellino, 83100, Italy; Jacob School of Biotechnology and Bioengineering, Sam Higginbottom Institute of Agriculture, Technology and Sciences, Allahabad, 211007, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Dubey
authors.affiliation: Istituto di Scienze dell'Alimentazione - CNR, Via Roma 64, Avellino, 83100, Italy; Dipartimento di Chimica e Biologia "Adolfo Zambelli", Università degli Studi di Salerno, Via Giovanni Paolo II 132, Fisciano, 84084, SA, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Marabotti
authors.affiliation: Jacob School of Biotechnology and Bioengineering, Sam Higginbottom Institute of Agriculture, Technology and Sciences, Allahabad, 211007, India.
authors.forename: Pramod W
authors.initials: PW
authors.lastname: Ramteke
authors.affiliation: Istituto di Scienze dell'Alimentazione - CNR, Via Roma 64, Avellino, 83100, Italy. Electronic address: angelo.facchiano@isa.cnr.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Facchiano
mesh_terms: D053818:Chymases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D020441:Ginkgo biloba / Q000737:chemistry; D046934:Ginkgolides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation
chemical_list: D004791:Enzyme Inhibitors; D046934:Ginkgolides; D053818:Chymases
keywords: Cardiovascular diseases; Chymase; Ginkgo biloba; Herbal nutraceutical; Inhibitor; Molecular docking; Screening