This proposal requests funds to permit Dr. Harold A. Scheraga, Professor of Chemistry, Cornell University, to pursue with Dr. Mu Shik Jhon, Professor of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), for a period of 24 months, a program of research to determine the free energies of hydration of model compounds that are prototypes of the side chain groups of proteins, and the free energies of interaction of various pairs of these molecules in water. In addition, the structure of water in solutions of these model compounds will be investigated, especially the nature of the hydrogen-bond network. An adaptive, importance sampling Monte Carlo algorithm, together with empirical pair-wise and three-body potentials based on ab initio quantum mechanical calculations, will be used. The results of this phase of the research will be used to calculate hydration free energies and the most stable conformations of polypeptides and proteins in aqueous solution. This research project involves the use of statistical mechanical and quantum mechanical calculations to determine the molecular geometry of polypeptides and proteins which are dissolved in water. The research results will contribute to a better understanding of solution chemistry. The collaborators are highly respected scientists who have acquired considerable expertise in the field of the project. They have developed a research plan in which responsibilities are shared, and the expertise of the one, in quantum mechanics, and the other, in statistical mechanics, will be combined and brought to bear on a problem of mutual interest and mutual benefit. This research problem is important, not only to theoretical chemistry, but also to medical sciences, where an understanding of protein and other biopolymer solutions may have a bearing on thrombosis and other cardiovascular abnormalities. This project is relevant to the objectives of the U.S.-Korea Cooperative Science Program which seeks to increase the level of cooperation between U.S. and Korean scientists and engineers through the exchange of scientific information, ideas, skills, and techniques and through collaboration on problems of mutual benefit.
