STRUCTURAL & DYNAMIC STUDIES OF PROTEINS BY NMR

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The proposed Physician Scientist training program will train the candidate in modern nuclear magnetic resonance (NMR) methods for evaluation of structure and dynamics of macromolecules, particularly proteins, and will deepen his appreciation of protein structure-function relationships. The candidate will later apply these techniques, together with his knowledge of enzyme kinetics, to the study of medically significant molecules within his chosen clinical area of pediatric hematology-oncology. The Phase I training program includes three graduate courses (structure and function of biological molecules, methods for their study, and enzyme kinetics and mechanism), NMR tutorial with the sponsor,and small projects which exploit ongoing research in the sponsor's laboratory and which span the major current areas of NMR. One of two projects will be undertaken during Phase II, with the choice to be determined by feasibility as assessed at the beginning of Phase II. Phase II project A involves a basic study of protein folding, and Phase II project B involves NMR and kinetic studies of a retroviral protease homologous to that from human immunodeficiency virus I. The candidate's long range goal is to use fundamental protein biophysics to contribute strategies for rational drug design.