Analysis of compounds isolated from gnetum gnemon L. Seeds as potential ace inhibitors through molecular docking and molecular dynamics simulations

Objective: Gnetum gnemon L. (melinjo) seed extracts have been known to have some biological activities. One of them is ACE (angiotensin-converting enzyme) inhibitor. The present study was conducted to predict potential ACE inhibitory activity of several compounds isolated from Gnetum gnemon L. seeds by using in silico method. Methods: In this study, several compounds isolated from melinjo seeds were determined for their ACE inhibitory activity through molecular docking study and molecular dynamics simulations. Molecular docking experiment was performed by using AutoDock4Zn. Subsequently, molecular dynamics simulations using AMBER within 20 ns was conducted to analyze the interactions stability between zinc-ligand and ligand-amino acids in the active site of ACE since both of these mechanisms were known to play essential roles to inhibit ACE. Results: The results showed that resveratrol, gnetol, isorhapontigenin, gnetin C, trans-ε-viniferin, gnemonol K, gnemonol M and aglycone of gnemonoside B exhibited ∆G values which were lower than or close to lisinopril, captopril, and enalaprilat. Some of these ligands were able to bind zinc ion via cation-pi interactions. According to the free-energy binding calculations using MM-GBSA and MM-PBSA methods, gnetin C showed the highest affinity for ACE among other ligands at a temperature of 300 K, while at a temperature of 310 K the highest affinity was exhibited by gnemonol K. Conclusion: According to the molecular docking and molecular dynamics simulations, several compounds isolated from melinjo seed showed potential ACE inhibitory activities, in which gnemonol K promised as the most potential compound to have ACE inhibitory activity.