MOLECULAR DYNAMICS SIMULATIONS OF SEVERAL SELECTED COMPOUNDS FROM THE HERBAL DATABASE OF INDONESIA RESULTS OF MOLECULAR DOCKING AGAINST DNA METHYLTRANSFERASE ENZYME

Objective: This study aimed to investigate the interactions of DNA methyltransferase (DNMT) enzymes and potential ligands as DNMT inhibitorsthrough molecular dynamics simulations.Methods: This study was conducted using tools in the form of hardware (primary and secondary computers) and software (OpenBabel, AutoDockTools, Amber MD, Amber Tools, VMD, PuTTY, LigandScout, and UCSF Chimera).Results: Results of molecular docking of cassiamin C, procyanidin B2, epicatechin-4alphaent-8-ent-epicatechin, epicatechin-4beta-8-epicatechin-3-O-gallate, neorhusflavanone, 3-O-galloylepigallocatechin -4beta-6-epicatechin-3-O-gallate, withanolide, 3-O-galloylepigallocatechin-4beta-6-epigallocatechin-3-O-gallate, cyanidin-3-6″-caffeylsophoroside-5-glucoside, epifriedelinol, gallocatechin-4alpha-8-epicatechin, scutellarein-7-glucosyl-1-4-rhamnoside, epigallocatechin-3-gallate (EGCG) (positive control), and sinefungin (co-crystal) compounds showed ΔG values −9.34,−10.95, −7.95, −11.01, −8.78, −8.87, −11.49, −7.98, −5.92, −8.92, −9.17, −8.76, −9.70, and −9.11 kcal/mol, respectively. Cassiamin C, procyanidin B2,epicatechin-4-beta-8-epicatechin-3-O-gallate, withanolide, and gallocatechin-4alpha-8-epicatechin compounds had lower ΔG than sinefungin (cocrystal)and EGCG (positive control) compounds. The results of molecular dynamic simulation of seven selected compounds showed the best overallactivities were procyanidin B2, epicatechin-4beta-8-epicatechin-3-O-gallate, and gallocatechin-4alpha-8-epi-catechin compounds.Conclusions: The best overall activities based on molecular docking and molecular dynamic simulation were procyanidin B2, epicatechin-4beta-8-epicatechin-3-O-gallate, and gallocatechin-4alpha-8-epi-catechin compounds. Amino acid residues that are important for the activity of DNMT1inhibitor are Phe1145, Glu1168, Met1169, Cys1191, Glu1266, Ala1579, and Val1580.