The Molecular Modeling Section uses and develops theoretical tools with which to study the forces that govern the structure and interaction of globular protein molecules, to study and predict the three-dimensional structure of these molecules, and to design protein molecules with new or improved properties. Following are some of the research activities and results that we obtained during this reporting period: (1) Major modifications were made to our interactive, graphics-based molecular modeling tool, GEMM, so that it can run in the multiple window environment. This saves time and resources since one workstation can now be used to do multiple graphics-oriented tasks. (2) We constructed a new theoretical model for hydrophobic hydration, according to which hydrogen bonds are stronger but also more broken at the surface of a hydrophobic molecule in water. This is important because hydrophobic hydration is widely considered to be the most important of the forces that govern the stability and interaction of proteins and other biological molecules. (3) We calculated cavity distributions in the protein structure and found a number of surprising characteristics of the distribution. We found, for example, that the hydrophobic core of a protein molecule is packed very tightly on the average, but their centers are also more likely to contain cavities. The full implications of this finding are yet to be explored, but we believe that this is a watershed finding, one that will turn out to have major implications on the stability and folding of protein molecules. (4) We investigated characteristics of a set of schemes for simplified representation of the protein backbone structure and devised a new, fast algorithm for constructing amide peptide groups once the alpha-carbon geometry of the protein backbone is known. These results will be used in our next generation ab initio protein folding program. We wrote two invited review articles during this year, one on the solvent reorganization and hydrophobicity and the other on the ab initio protein folding technique. In addition, the PI and Dr. Jean Garnier, a Fogarty scholar, organized a major international conference on Protein Folding and Design, which was held in April on NIH campus. There were 47 speakers, 221 posters, and 1,023 attendees from 29 countries.
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