QSAR studies of angiotensin converting enzyme inhibitors using CoMFA, CoMSIA and molecular docking

• Main Authors: Tong Jian-Bo, Wang Tian-Hao, Feng Yi, Jiang Guo-Yan
• Format: Article
• Language: English
• Published: Serbian Chemical Society 2021-01-01
• Series: Journal of the Serbian Chemical Society
• Subjects: ace inhibitors; 3d-qsar; new drug design; molecular docking
• Online Access: http://www.doiserbia.nb.rs/img/doi/0352-5139/2021/0352-51392000072T.pdf
• ISSN: 0352-5139; 1820-7421

In order to better understand the biochemical interactions governing their activities in lowering blood pressure, multiple quantitative structure-activity relationship (QSAR) models were developed from a data set of 58 angiotensin converting enzyme (ACE) inhibitors. The models were built by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. The best CoMFA model had a cross-validation q2 value of 0.940, a non cross-validation r2 value of 0.952 and an external validation statistic Qext 2 value of 0.920. For the best CoMSIA model the values were with q2 = 0.872, r2 = 0.926 and Qext 2 = 0.868. Based on the contour maps, eight new ACE inhibitors were designed. Molecular docking was employed to further explore the binding requirements between the ligands and the receptor protein which included several hydrogen bonds between the ACE inhibitors and active site residues. This study showed extensive interactions between ACE inhibitors and residues of HIS383, GLU384, HIS513, TYR520 and LYS511 in the active site of ACE. The design of potent new inhibitors of ACE can get useful insights from these results.