The Biophysics of BPTI Folding Mutants

这项工作的广泛和长期目标是阐明支配蛋白质折叠的规则。牛胰腺胰蛋白酶抑制物(BPTI)是一种简单的球状多肽，具有大量的结构生物物理活性，对于野生型蛋白已有理论数据，因此被选为模型系统。基本的推力将是大量生产具有干扰折叠特性的转基因形式的BPTI，并从生物物理学的角度对其进行表征。具体的研究重点是：1)通过使BPTI突变体缺失两个或两个以上的天然二硫键来解决“设计出”二硫键的问题。2)促进合作者实验室中选定的BPTI突变体的结构和动力学方面的工作。这种遗传学和生物物理学相结合的方法来剖析一个非常简单的模型蛋白质的折叠机制，应该有助于阐明仍然知之甚少的蛋白质折叠过程。

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.