Developing a Simulation Framework for Modeling Biomolecules in Ionic Liquids

First, we describe the development of a protocol to quickly parameterize and validate ionic liquid force fields. Simulations that use these force fields are shown to accurately predict several thermopysical properties of ionic liquids. When compared to other solvent force fields, our force fields perform similarly well or better than many commonly used models for the prediction of solvent properties. Second, simulations containing enzymes solvated in ionic liquids and water are discussed. The mixture of ionic liquids and proteins is of interest because non-native solvents have been shown to affect the function of enzymes in both positive and negative ways. Yet, there is an incomplete understanding of the reasons why ionic liquids have such effects on proteins. The studies presented in this document focus on several different ionic liquid-enzyme systems and the ways in which the solvent affects the structure and dynamics of the solute. We also employ enhanced sampling techniques such as metadynamics to extend our understanding of the thermodynamics of ionic liquid-protein interactions. Third, we study systems that involve the self-assembly of biomolecules in ion-rich environments. One group of interesting peptides are the leucine-lysine (LK) peptides. LK peptides vary in secondary structure depending on the periodicity of their sequences, and often they have clearly separated hydrophobic and charged sides. LK peptides are known to precipitate silica bionanoparticles from silicic acid solutions. Our simulations probe the structures of LK peptide aggregates and the formation of silicic acid structures at ordered LK peptide interfaces. In addition to LK peptides, we also study the formation of metal ion-surfactant complexes in organic solvents. The morphology of these complexes can be predicted using molecular dynamics, and our simulation results compare well with experimental data. Altogether, our simulations demonstrate that molecular dynamics simulations of biomolecules in the presence of ionic liquids and other complex ions is a viable tool to understand solvent-solute interactions and that the results of such simulations compare well to available experimental data. We believe that the methods we have developed in this dissertation can be extended to study almost any commonly available solvent with almost any biomolecule.