(178v) Simulations of Biomolecules in Nonaqueous Solvents

Simulations of biomolecules give us insight into the atomistic and molecular level properties of a variety of substances including proteins, ligands, drugs, biomass, and small organic molecules. Many important processes that involve these classes of materials necessitate the use of nonaqueous solvents. Unfortunately until now, there have been few systematic studies of these substances in any media but water. We have begun simulating biomass and enzymes in solvents that include alkanes, aromatics, and ionic liquids. Such simulations prove difficult in their construction and execution for a few reasons. First, force fields that are complementary to protein and biomass force fields must be developed in order to properly conserve energy and dynamics. Second, the thermodynamic and structural properties of the solvent must conform to experimental observations. Third, new techniques for constructing simulation boxes must be employed. After these three obstacles are overcome, one may finally begin a rigorous computational study.

We have modified a number of popular and standardized computational packages in order to systematically develop force field parameters for nonaqueous solvents, to simulate systems in exotic media, and to compute properties of the systems in which we are interested. Three unique but related simulation systems will be discussed. First, xylanase and cellulase have been shown to remain partially active in low concentrations of ionic liquids in water. We have explored the reasons why some enzymes remain more active than others when introduced to foreign solvents. Much of the difference appears to depend on the dynamics of the protein motion and its effects on the ability of the enzyme to bind its substrate properly. Second, cellulosic biomass is highly recalcitrant. It remains as a highly stable mix of cellulose, hemicellulose, and lignin even at high temperatures. Ionic liquids can help to detangle this matrix of biomass and expose more area to attack by enzymes. We have determined some molecular properties that allow many ionic liquids to perform this function while others fail completely. Third, once the long chain polysaccharides that constitute cellulose or hemicellulose are free in solution, they tend to occupy new conformations in different solvents. We have found the free energy surfaces of several internal angles of biomass in ionic liquids and compared them to the aqueous case and QM/MM calculations. This can have important implications in how enzymes bind and hydrolyze cellulose or hemicellulose. By developing systematic ways of simulating enzymes and polysaccharides in exotic solvents, we hope to open a wide range of opportunities to answer questions that were previously beyond the scope of much of the simulation community.