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

Shabnam      Pourhanafi; Vildan   Adar   Gürsoy

doi:10.2174/1570180819666220602090408

Abstract

Background: Antiplatelet drugs are key tools for the prevention and elimination of cardiovascular diseases. 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.

Keywords: Antiplatelet, phytochemicals, molecular docking, molecular dynamics simulation, binding free energy, ADMET.

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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1570180819666220602090408	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X

Letters in Drug Design & Discovery

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

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