MODELING HYDROPHOBIC AND HYDROPHILLIC INTERACTIONS

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Molecular modeling is fast becoming an important tool in chemistry and biochemistry. Useful force fields, and friendly molecular mechanics and molecular dynamics programs are available, and these methods play a very important role in computer aided molecular design(CAMD). There is a wide separation of time scales and both short and long range forces in these systems. A major objective of this proposal is to apply Multiple Time Scale Methods recently discovered in my group to the acceleration of biomolecular simulations. Protein folding and membrane formation, among other things, depend crucially on how water molecules interact with each other and with chemical groups on chain molecules. It is becoming clear that the simple fixed charge two-body electrostatic water potential models already in use in biological simulations and in CAMD ignore important effects, and may overestimate solvent separated hydrophobic pairs over contact pairs. These models also cannot describe ion hydration accurately. Another important objective of this proposal is to devise accurate potential models for water and more complex molecules that allow atomic charges to change in response to a changing chemical environment. The goal is to be able to model interfacial properties of water, the hydrophobic effect, and ionic hydration accurately with one self- consistent potential model. The proposed models contain all of the important effects left out in current two-body electrostatic models routinely used in simulations. With this new model we propose to study hydrophobic aggregation, water induced chain folding, micelle formation, and the solvation of ions. The proposed research will provide new methods and algorithms for use in biological simulations.