Molecular design of inhibitors for RNA methylation regulating enzymes

Abstract

The RNA m6A methylation plays crucial role in various physiological processes and therefore the development of chemical agents controlling this process has large biological and medical importance. In the present work, the results of the computational design of the inhibitory ligands for the enzymes regulating the RNA adenosine N6-methylation are presented. The structure of the enzyme-ligand complexes was established using the molecular docking and molecular dynamics approaches. The activity of the best predicted RNA m6A methyltransferase inhibitors was confirmed using enzyme inhibition and cell proliferation assays. These compounds are the first known RNA m6A methylation inhibitors and therefore of substantial interest for further biomedical studies.