Interaction of human chymase with ginkgolides, terpene trilactones of Ginkgo biloba investigated by molecular docking simulations

• Published in: Biochemical and biophysical research communications Vol. 473; no. 2; pp. 449 - 454
• Main Authors: Dubey, Amit, Marabotti, Anna, Ramteke, Pramod W., Facchiano, Angelo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.04.2016
• Subjects: Cardiovascular diseases; Chymase; Chymases - antagonists & inhibitors; Chymases - chemistry; Chymases - metabolism; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Ginkgo biloba; Ginkgo biloba - chemistry; Ginkgolides - chemistry; Ginkgolides - pharmacology; Herbal nutraceutical; Humans; Inhibitor; Molecular docking; Molecular Docking Simulation; Screening; Ginkgo biloba; Screening; Herbal nutraceutical; Inhibitor; GB; Cardiovascular diseases; Molecular docking; OHH; Chymase; PDB
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.03.028

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. •Ginkgo biloba compounds were investigated by in silico approach as potential chymase inhibitors.•Four best compounds have been selected and compared to known chymase inhibitors.•Potential development of new drugs has been proposed in consideration of protease specificity.