Molecular Docking, Dynamics Simulation, and Physicochemical Analysis of Some Phytochemicals as Antiplatelet Agents

Abstract

Background: Antiplatelet drugs are key tools for the prevention and elimination of cardiovascular disease. However, currently available agents are associated with a variety of adverse effects, and new therapeutically effective drugs with fewer or no side effects are urgently needed for effective medication. Objective: The present in silico research aimed to determine the inhibitory potential of 50 phytochemicals on platelet function using computational methods. Methods: The compounds first were subjected to molecular docking analysis with five chosen antiplatelet targets and the best compound with the lowest energy against each target was selected and analyzed in detail. These complexes were then considered for molecular dynamics simulation and binding free energy analysis. SwissADME and ADMETlab servers were also used to evaluate their drug-likeness and ADMET properties. Results: Ligands that exhibited the lowest energy with the corresponding target were: graveolinine against COX-1, sanguinarine against P2Y12 and PDE-3, rutin against GP-VI, and bisdemethoxycurcumin against PAR-1. Simulation of these complexes affirmed the binding stability between the ligands and the proteins. Root mean square deviation and root mean square fluctuation showed that in the case of PAR-1- bisdemethoxycurcumin, some fluctuations were observed during the simulation process. Calculation of the binding free energy indicated that in all systems, the van der Waals energy made a significant contribution to the binding and stability of the system. Conclusion: The result of this study could provide useful insights into the development of new lead antiplatelet agents.