Unraveling enzymatic mechanisms by means of computational tools: biotechnological implications in the study of glycosidases

Abstract

The growth of glycomics (a field analogous to genomics or proteomics but focused on glycosides) and the development of diagnostic tests, vaccines and new therapeutics based on carbohydrates are hampered by the lack of effective tools for their production. Enzymatic synthesis, characterized by its high stereo- and regioselective products obtained under mild conditions, is a promising approach to solve this problem. In this regard, retaining glycoside hydrolases (GHs) have a high potential to be engineered to synthesize carbohydrates by transglycosylation. The conversion of GHs into TGs, i. e. from enzymes that perform hydrolysis to enzymes that perform synthesis, has received great attention in the last few years. Nevertheless, the lack of enzyme structures and the limited knowledge of the molecular basis of transglycosylation is hindering rational design of TGs. In this work, we show how theoretical chemistry and first principles molecular dynamics simulations can provide fundamental insight for the production of such valuable enzymes.

Keywords: Enzymatic catalysis, carbohydrates, glycoside hydrolases, molecular dynamics, computational chemistry, QM/MM approach.