11-02: Molecular Simulation of Biomolecules in Non-Aqueous Media: Application to Lipase and Glycoside Hydrolase

Ionic liquids may revolutionize bioprocess efficiency and economics in enzymatic pretreatment of biomass.  Incomplete understanding of the relationship between solvent, enzyme structure, and reactivity has hampered these efforts.  We lack the ability to relate molecular features of the solvent to its effect on enzyme stability and activity.  In cases where solvents lower the activity of the enzyme, we do not have the tools to systematically understand the root cause of the loss of activity or how to effectively use mutagenesis techniques to overcome the activity loss. This talk describes our efforts to study biomolecular structure and dynamics of two enzymes (Candida Rugosa Lipase A (CRLA) and glycoside hydrolase (GH) 11) in four different ionic liquids and nonpolar organic solvents (for lipase).  We use classical MD simulations to probe the solvent structure and equilibrium fluctuations.  These results are used to understand enzyme deactivation that was observed in our lab with various experiments.  To describe the enzymes and biomolecules we use the AMBER99SB force field and the ionic liquid simulations are performed with the generalized amber FF (GAFF).  Simulations of pure IL show good agreement with experimentally measured heat capacities and densities.  The simulations of lipase with several solvents show that the ionic liquid solvents strongly stabilize the enzyme compared to water or even nonpolar alkane and aromatic solvents.  In addition to changes in the entire enzyme structure, we observe significant changes in key regions of the CRLA RMSF related to enzyme activity, whereas in GH11 comparatively few structural changes are observed.