Theoretical Studies of Protein Folding

这项工作是对蛋白质折叠问题的三部分攻击。首先，这个问题的统计力学将被阐明。简化的蛋白质晶格模型（具有现实但易于计算的程序）将用于提供蛋白质折叠问题的基本统计力学见解。熵采样蒙特卡罗方法（由构象偏倚链再生过程和跳跃行走方法增强）用于确定蛋白质的状态密度，由此减少了与构象和折叠相关的性质。该方法被推广到离晶格处理。其次，为了能够以能量作为判别多维能量面中全局极小值与其他局部极小值的标准（即所谓的多重极小值问题），正在开发一种新的力场。第三，用扩散方程方法克服了多重极小问题。这种理论方法将提供对蛋白质折叠特性的基本理解。这个问题目前处于蛋白质研究的前沿。要获得的基本理解将适用于生物技术行业。最后，这种方法将为进行这项研究的研究助理提供培训，也为与这些研究助理一起工作的几名研究生提供培训。＊＊＊

9513167 Scheraga This work is a three-part attack on the protein folding problem. First, the statistical mechanics of the problem will be elucidated. Simplified lattice models of proteins (with realistic but easily computable procedures) will be used to provide fundamental statistical mechanical insight into the protein folding problem. The Entropy Sampling Monte Carlo method (augmented by a conformational-biased chain regrowth procedure and a jump-walking method) is used to determine the density of states of the protein, from which the properties related to conformation and folding are reduced. The method is being extended to an off-lattice treatment. Second, in order to be able to use energy as a criterion to distinguish the global minimum from other local minima in the multidimensional energy surface (the so-called multiple-minima problem), a new force field is being developed. Third, the multiple-minima problem is being surmounted by the diffusion equation method. %%% This theoretical approach will provide the basic understanding of the folding properties of protein. This problem is currently at the frontier of protein research. The basic understanding to be acquired will be applicable to the biotechnology industry. Finally, this approach will provide training for the research associates carrying out this research, and also for several graduate students working together with these research associates. ***