Investigating the protective effects of carbohydrate coatings on the structure and dynamic of l‐asparaginase against heat stress; a molecular dynamic simulation

Abstract l -asparaginase is one of the most important and widely used drugs in the treatment of leukemia. Like other proteinous drugs, this enzyme suffers from difficulties in the out-of-body storage/transportation and in vivo, which can be assisted by drug delivery systems prepared with various biodegradable materials. In this study, the interactions and temperature stabilization effects of five common carbohydrate biopolymers were investigated using computational molecular dynamic simulation. For this purpose, the l -asparaginase protein in free state and in complex with pectin, alginate, hyaluronic acid, inulin and chitosan was studied at two temperatures of 300 and 363 K. The results of molecular modeling showed that the increasing of temperature leads to instability in dynamic and structure of l -asparaginase. Among different studied polysaccharides, hyaluronic acid and inulin had more protective effect on protein structure at high temperature than others. In contrast, chitosan and alginate represented less ability to maintain protein structure under heat stress. Finally, according to the findings of this study, it is suggested that hyaluronic acid and inulin polysaccharides can be good candidates for preparing the pharmaceutical formulation of l -Asparaginase in order to preventing its structural denaturation at higher temperatures.