Molecular docking study of vemurafenib derivatives on melanoma inhibitory activity (MIA) as anti-melanoma

Abstract

Background: Melanoma is one of the cancers with high mortality rates in Indonesia. The newest potential anti-melanoma target is the Melanoma Inhibitory Activity (MIA/5IXB) macromolecule, but the location of the binding pocket interaction is unknown. Vemurafenib is known to be active in vivo as against melanoma. Thus, it can be used as a lead compound. This study aimed to examine the location of the binding pocket and the interactions that occur between macromolecules and the test compounds. Methods: It was carried out using the blind docking method between vemurafenib and an MIA macromolecule. Results: The results showed that the best molecular docking was obtained in the distribution of the grid box area in the third area with a ∆G value of -7.80 kcal/mol. Docking validation results showed the value of ∆G 11.06 kcal/mol with an average value of RMSD 1.788 Å, and the amino acid residues that played a role in the interaction were MET31, TYR30, and PRO33. Targeted docking to the binding pocket results on 45 test compounds showed that the most potent compound was Compound-17 with a ∆G value of 11.31 kcal/mol with hydrophobic bond interactions on amino acid residues TYR30. This hydrophobic bond is responsible for the MIA mechanism as an inhibitor of melanoma cell metastasis in the body. It can be concluded that the binding pocket of the MIA(5IXB) macromolecule with the vemurafenib compound is at the amino acid residues MET31, TYR30, and PRO33 with the interaction of hydrogen bonds and hydrophobic bonds. Also, it was observed that T.C-17 is the most potential anti-melanoma test compound.