STRUCTURAL DYNAMICS AND SOLVATION OF THE β-GLUCOSIDASE FROM HUMICOLA INSOLENS (BGHI) IN AQUEOUS SOLUTIONS CONTAINING GLUCOSE

The enzyme β-glucosidase (BG) is a glycosyl hydrolase (GH) that is involved in the lignocellulose deconstruction and is of crucial importance for industrial processes, such as the manufacturing of second generation (2G) bioethanol. It is well known that the BG, that breaks down the β-1,4 linkage of cellobiose, is inhibited by glucose (its own reaction product) at high concentrations due to a competitive inhibition process. However, at lower glucose concentrations, the β-glucosidase from Humicola insolens (BGHI) undergoes an activation process that is not yet fully understood. Sugar molecules tend to favor the protein structure hydration in aqueous solutions, which generally promote its stabilization and, therefore, our guess is that this activation phenomenon may be due to indirect effects induced by the solvent arrangement around the protein. Here, we report the partial results obtained for the first part of a computational study that aims to investigate the interplay between protein and solvent structural dynamics, which is very challenging to address through experiments. We have performed atomistic classical Molecular Dynamics (MD) simulations of BGHI at different glucose concentrations combined with a detailed examination of the solvent environment based on Minimum Distance Distribution Functions (MDDF) calculations and Kirkwood–Buff (KB) solution theory. The results allowed us to obtain the preferential solvation parameter (Γ) for the solvent components and elucidate the solvation structure of the protein. We could also identify the main interactions between the protein and the co-solvent molecule, as well as map the most flexible regions of the BGHI. Finally, the MD simulations also provided structures that will be employed as a starting point for future multiscale simulations (QM/MM).