Evaluation of inhibitory affinity potential of the alkaloids against crystal structure of human angiotensin-converting enzyme using Lamarckian genetic algorithm

Abstract

Angiotensin-converting enzyme (ACE) is known to be key factor for hypertension. Alkaloids are the principal constituents that may play a crucial role in the management of hypertension. The current objective of the study is to identify inhibitory affinity potential of the certain commercially available alkaloids, against crystal structure of human angiotensin-converting enzyme (4APH) using AutoDock 4.2. In this perspective, alkaloids like quinidine, quinine, tubocurarine, vinblastine, vincamine, vincristine and yohimbine were selected. Captopril, a known ACE inhibitor was used as the standard. All the selected compounds were analysed for Lipinski’s rule of five. In the docking studies, conformational site analysis and docking parameters like binding energy, inhibition constant and intermolecular energy were determined using AutoDock 4.2. The selected compounds and the standard showed the following amino acid residues are responsible for the inhibitory affinity potential ASP 1, ARG 2, VAL 3, TYR 4, ARG 522 along with hydrogen bonding interactions. The selected compounds exhibited the binding energy ranging between −9.56 and −5.82 kcal/mol when compared with that of the standard (−5.38 kcal/mol). Inhibition constant (97.64 nM to 53.96 μM) of the alkaloids also coincide with the binding energy. The compounds exhibited the intermolecular energies ranging between −11.40 and −9.14 kcal/mol. The current molecular simulation study predicted the ACE inhibitory activity of the selected compounds. Hence, these compounds can be further evaluated to develop potential chemical molecules for the prevention and management of hypertension.