Heterogeneous solvation shell dynamics around candida antarctica lipase b enzyme using molecular dynamics simulations: relationships with solvent structure, enzyme structure and enzyme dynamics

Abstract

Solvent-compatible enzymes (those that function in organic solvents) are an important field of research. Understanding the relationship between solvent dynamics and protein dynamics will improve applications of proteins in non-aqueous solvents and design of solvent systems and engineer proteins for non-aqueous biocatalysis. The main focus of this dissertation is characterization of local heterogeneous solvation shell dynamics around Candida Antarctica Lipase B (CALB) enzyme and relating these local solvation shell dynamics to solvent structure, enzyme structure and enzyme dynamics. Solvent dynamics were studied under two categories, as hydration layer dynamics and non-aqueous solvation layer dynamics. Interfacial solvent dynamics at the CALB enzyme have been characterized by protein-solvent hydrogen bond lifetimes, solvation layer residence times, reorientation times, and diffusion times of solvation shell solvent molecules. We have shown that local water dynamics are affected by the protein structure directly through chemical heterogeneity and topological heterogeneity of protein structure and indirectly, since the protein structure modulates the local water structure and these changes in local water structure affect the local water dynamics. Further we have shown that protein structure influences protein dynamics by modulating the local solvent structure and providing regions with faster moving water. Validity of Rosenfeld scaling, which describes the diffusion-entropy relation in liquid water was discovered for waters in local hydration shell for the first time in this study. As non-aqueous solvents, a variety of solvents are used in this study; namely, acetonitrile, n-butanol, tert-butanol, and cyclohexane, and we have shown that that local solvent dynamics have effects on the local protein flexibilities and these effects depend on the nature of the solvent.