Structural insights into the binding mode of d-sorbitol with sorbitol dehydrogenase using QM-polarized ligand docking and molecular dynamics simulations

Abstract Gluconobacter oxydans is an organism involved in the incomplete oxidation mechanism of many sugars and alcohols. G. oxydans is involved in the biotransformation of d -sorbitol to l -sorbose via a membrane-bound d -sorbitol dehydrogenase (SDH). The focus of this study was to investigate the binding of d -sorbitol to SDH and determine the amino acids involved in the formation of l -sorbose. In order to determine the crucial interactions of d -sorbitol with SDH, in silico polarized ligand docking was employed. QM/MM-based interaction studies suggested that His302, Met366, and Asp368 actively participate in d -sorbitol binding. MD simulation-based mutational studies confirmed that these amino acids are key residues in the binding of d -sorbitol. In particular, mutation of His302 resulted in the denaturation of protein structure and loss of stability. Overall, our results suggest that the role of His302 is to hold the d -sorbitol, and future replacement of polar amino acids in a surrounding pattern will be helpful to increase the production of sugars by G. oxydans.