Molecular Dynamics Study of the Effect of Induced Mutations on the Protein Structures Associated with Diseases of A Radiobiological Nature

Abstract

The induced mutations in biological molecules, such as DNA and proteins, have quite a different nature (environmental factors, viruses, ionizing radiation, mutagenic chemicals, inherited genetic alterations, etc.). Induced mutations can destroy the existing chemical (hydrogen) bonds in the native molecular structures or, on the contrary, create new chemical (hydrogen) bonds that do not normally exist there. In protein structures, the cause of such changes might be the substitution of one or several specific amino acid residues (point mutations). At the atomic level, the replacement of one amino acid residue by another causes essential modifications of the molecular force fields of the environment, which can break important hydrogen bonds underlying the structural stability of biological molecules. In this work, based on molecular dynamics (MD) method, we demonstrate the effect of mutational structure changes on several biological protein models (the p53 oncoprotein, visual pigment rhodopsin, cyclin-dependent kinase, and recA protein). Molecular dynamics simulation is a powerful tool in investigating the structure properties of biological molecules on the atomic and molecular levels, and it has been widely used to study the structural conformational behavior of proteins. We also discuss the scenario of the mutation effects associated with different kinds of diseases that could develop and take place in physiological conditions.