Molecular insight and resolution for tumors harboring the H-ras(G12V) mutation

Abstract

A study about the physiological regulators of oncogenic growth has recently been published in the literature. When the H-ras gene mutates, the mutant H-ras(G12V) protein causes uncontrolled cell growth. We tried to observe whether there is any difference between the wild type and mutant H-ras protein in terms of the molecular character and structural variation in silico. Our hypothesis is that the H-ras(G12V) protein, accompanied by an altered structure, might be responsible for excess signal transduction and even tumor formation. In this study, we wanted to find a potent compound that could bind to the H-ras(G12V) protein and interfere with the phosphorylation of the substrate protein. By using homology modeling, structure-based docking, candidate screening, and molecular dynamics (MD) simulations, we demonstrated that the structural and molecular character of the H-ras and H-ras(G12V) proteins were different. Abrine could bind to H-ras(G12V) and might interfere with the phosphorylation process. These results provided novel insight for the management of tumors or cancers, which harbor the H-ras(G12V) mutation.