-The computational study of a 3D model of the hyaluronidase interaction with shortchain glycosaminoglycan ligands demonstrated the diversity and significance of their reaction on enzyme structure. Exploratory computational consideration of the interaction of a 3D model of bovine testicular hyaluronidase (BTH) with short chain glycosaminoglycan ligands demonstrated the diversity and significance of their effect on the structure of the enzyme. The reported impact was due to electrostatic noncovalent interactions (without specific binding to the active site), causing noticeable conformational changes in the molecule biocatalyst/enzyme. As a result of this, the inactivation and stabilization of the enzyme globule are observed, and a change in its inhibition by heparin. The binding of chondroitin trimers (on centers cs2, cs4, cs7, cs8 or cs1, cs2, cs4, cs7, cs8) decreased the inhibition of the enzyme by tetramer heparin. The importance of ligand binding for the regulation of the functioning of the enzyme and the presence of a diverse and multicomponent microenvironment of the biocatalyst is noted. The sequence of preferential coupling of ligands with hyaluronidase is elicited in our study making it possible to evaluate the feasibility of achieving experimental selective modification of the enzyme (possibly noncovalently or covalently, for instance, with chondroitin sulfate trimers on centers cs7, cs1, cs5) for potential experimental production of stabilized forms of the enzyme. Promising approaches are noncovalent effects on hyaluronidase of chondroitin or chondroitin sulfate trimers, as well as covalent modification of the biocatalyst with chondroitin sulfate trimer or the production of genetically engineered derivatives of the enzyme. The mentioned changes in the structure of hyaluronidase may contribute to the implementation of its directed experimental design for subsequent biomedical research and practical clinical trials.
