Theoretical Studies of Protein Folding

Scheraga博士正在进行一项实验和理论相结合的研究项目，旨在阐明多肽链折叠成蛋白质天然构象的能量和机制，以及由此产生的蛋白质（酶或激素）对底物或受体的作用。虽然目前的电位函数对于他所做的一些应用来说已经足够精确，但他对这些电位（以及文献中的其他电位）的分析表明，是时候对潜在形式（以及电位的参数化）进行全新的审视了；这是拟议工作的第一个目标。其次，已经开发了一些非常成功的方法来克服小多肽的多重极小问题，他将致力于改进这些方法，并将其推广到含有100个残基的球状蛋白质。他将在crambin和牛胰蛋白酶抑制剂上测试该方法，然后用它们来计算干扰素的结构。他也将处理纤维蛋白的大集合，即胶原蛋白。

Dr. Scheraga is carrying out a combined experimental and theoretical research program designed to elucidate the energies and mechanism of the folding of a polypeptide chain into the native conformation of a protein, and of the action of the resulting protein (enzyme or hormone) on a substrate or receptor. While current potential functions are sufficiently accurate for several of the applications that he has made, his analysis of these potentials (and also of others in the literature) indicates that it is time for a completely new look at the underlying form ( and parameterization of the potentials); this is the first goal of the proposed work. Secondly, some very successful methods have been developed to surmount the multiple-minima problem for small polypeptides and he will devote his efforts to improving them, and extending them to globular proteins containing of the order of 100 residues. He will test the methods on crambin and bovine pancreatic trypsin inhibitor, and then use them to compute the structure of interferon. He will also treat large assemblies of fibrous proteins, viz. collagen.