Molecular dynamics and solvation structures of the β-glucosidase from Humicola insolens (BGHI) in aqueous solutions containing glucose

The β-glucosidase enzyme is a glycosyl hydrolase that breaks down the β-1,4 linkage of cellobiose. It is inhibited by glucose at high concentrations due to competitive inhibition. However, at lower glucose concentrations, the glucose-tolerant β-glucosidase from Humicola insolens (BGHI) undergoes stimulation. Proteins, in aqueous sugar solutions, tend to be preferentially hydrated, which generally promotes their stabilization. Thus, solvation phenomena may contribute to both glucose tolerance and stimulation processes. We have performed atomistic classical Molecular Dynamics (MD) simulations of BGHI at different glucose concentrations to mimic the conditions found in the catalytic experiments. A detailed examination of the solvent environment through the calculation of minimum distance distribution functions (MDDFs) and Kirkwood-Buff (KB) integrals was performed. The enzyme is preferentially hydrated in the presence of glucose at all concentrations. Nevertheless, the hydration does not prevent the glucose from directly interacting with the BGHI surface or from entering the active site. Based on the obtained results, we hypothesize that preferential hydration is beneficial for enzyme activity. At the same time, product inhibition has little effect at lower concentrations of glucose, and at higher glucose concentrations, competition for the active site becomes predominant and the enzyme is primarily inhibited.