STRUCTURAL STUDIES OF BPTI FOLDING MUTANTS

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The goal of this project is to achieve a better understanding of how protein folding pathways are determined by amino acid sequence. This problem has recently become extremely important in biomedical research because the emergence of techniques for gene-sequencing has produced the sequence of hundreds of proteins whose three-dimensional structure is not known. A more complete understanding of protein folding will improve our ability to predict protein structure from sequence, providing structural insight into the function of the many gene products that play important roles in human disease. The work described in this proposal seeks to explain, in structural terms, the folding kinetics of bovine pancreatic trypsin inhibitor (BPTI). This will be done using a recently developed peptide model of a BPTI folding intermediate called P(alpha)P(beta)2. The native structure and dynamics of several mutants of BPTI that display altered folding kinetics will also be studied. The principle structural method to be employed is two dimensional nuclear magnetic resonance (2D-NMR). This method is capable of providing high resolution structural information for molecules in solution.