MOLECULAR DOCKING AND MOLECULAR DYNAMIC STUDIES: SCREENING PHYTOCHEMICALS OF Acalypha indica AGAINST BRAF KINASE RECEPTORS FOR POTENTIAL USE IN MELANOCYTIC TUMOURS

Abstract

Melanocytic tumors are a type of cancer that is most commonly found on the skin. The melanoma prevalence rate has risen dramatically over the last 50 years. As a result, the discovery of new therapeutic agents is critical. The BRAF kinase is one of the receptors involved in cell apoptosis. Dabrafenib is a selective BRAF inhibitor with common side effects such as rash, photosensitivity, and hyperkeratosis. Meanwhile, Acalypha indica is a plant that has been widely reported as a source of antiproliferative and proapoptotic compounds. However, the phytochemicals in A. indica that play an important role in melanocytic tumors have yet to be discovered. Molecular docking is a structure-based drug design method that is used to identify potential hits during the drug discovery process. The aims of this study are to obtain candidate lead compounds for BRAF kinase based on binding mode interaction and binding stability by using AutoDock 4.2 and GROMACS 2019.6, respectively, for molecular docking and molecular dynamics (MD). The native ligand, SM5, has estimated free energy of binding and an inhibitory constant of -5.93 kcal/mol and 45.30 µM, respectively. 2-Methyl anthraquinone, chrysin, stigmasterol, and γ-sitosterol have higher binding energy, with an estimated free energy of binding of -6.24, -6.67, -6.35, and -6.14 kcal/mol, respectively. According to the MD simulation, stigmasterol and γ-sitosterol will be more effective at stabilizing the 6XFP complex during 100 ns. Finally, stigmasterol and γ-sitosterol are potential lead compounds as BRAF inhibitors.