The Biophysics of BPTI Folding Mutants

点击翻译按钮获取中文摘要

The broad, long-term objective of this work is to elucidate the rules that govern protein folding. Bovine pancreatic trypsin inhibitor (BPTI) has been chosen as a model system because it is a simple globular polypeptide, and a large amount of structural biophysical, and theoretical data is already available for the wild type protein. The basic thrust will be to produce, in quantity, genetically-modified forms of BPTI that have perturbed folding properties and characterize these biophysically. Specific Research priorities are: 1) Address the problem of "designing out" disulfide bonds by making BPTI mutants missing two or more of the native disulfides. 2) Facilitate work in collaborators' laboratories on the structure and dynamics of selected BPTI mutants. This combined genetic and biophysical approach to the dissection of the folding mechanism of a very simple model protein should help illuminate the still poorly-understood process of protein folding.