Study of binding of inhibitor molecules to the active site of protein kinases by method of molecular dynamics

Eukaryotic protein kinases are represented by a large superfamily of homologous proteins similar in structure of the catalytic (kinase) domain, consisting of 250-300 amino acids [3]. Most human protein kinases share a common fold consisting of an N-terminal lobe, consisting of a five-stranded β-sheet with an α-helix called the C-helix, and a C-terminal lobe comprising six α-helices. The active center is located between the two lobes and forms binding sites for adenosine triphosphate (ATP) and protein [4]. Protein kinases modify the functions of other proteins by phosphorylation, acting as elements of signaling pathways. Disorders and abnormalities in the activity of these enzymes give rise to the pathogenesis of many malignant neoplasms. Based on this fact, the targeted synthesis of some substances capable of selectively modifying the activity of protein kinases is an urgent task. The study of the process of interaction of molecules with the catalytic center of protein kinase by the method of molecular dynamics makes it possible to search for chemical structures of substances capable of inhibiting this enzyme [2]. Taking into account the high similarity of the structure of the catalytic domains of various human protein kinases, it is of scientific interest to develop a technique for modeling the molecular dynamics of the ligand-enzyme system, which allows predicting the spectrum of inhibitory activity against a set of protein kinases.