Theoretical Research of Interactions Between Glycosidases and Glycosaminoglycan Ligands with Molecular Docking and Molecular Dynamics Methods

Abstract

Computational methods have proved to be sometimes a single tool available for investigation of glycosaminoglycan-protein interactions. A two-stage process including molecular docking with its subsequent detalization using the methods of molecular dynamics is a prospective approach to theoretical modeling of protein-glycosaminoglycan complexes. This review deals with specific features of protein-glycosaminoglycan interactions studied by computational methods, docking and scoring function algorithms, and the use of molecular dynamics results with short-time (ps and ns) changes for processes developing within much longer time scales (ranging over several orders of magnitude). The data obtained with help of computational methods contribute the disclosure of biological interaction mechanism, elaboration of enzyme activity control and grounding of rational recommendations for novel therapeutic means development of high-molecular sort. The results of molecular docking of heparanase, chondroitinlyase ABC, chondroitinase B, and hyaluronidase were shown. The approach to productive design of molecules of compounds (regulating enzyme activity for novel drug derivative obtaining) is representative. The investigations of such kind are directed on ascertainment of action mechanism of these agents in biosystems for production of high efficacy of drug preparations of enzyme nature. It is shown that the molecular dynamics method provides modeling of all degrees of freedom in a protein-ligand complex and draws special attention to protein structure flexibility as a considerable challenge in the development of molecular docking. Computational data are reviewed in the aspect of complex formation between proteins and glycosaminoglycan ligands.