STRUCTURE BASED PREDICTION OF CONFORMATIONAL & BINDING FREE ENERGIES

这项提案中描述的研究目标是 构象自由能和结合自由能的计算 与生物大分子的结构和功能有关的。 涉及利益的具体问题包括确定 稳定的蛋白质折叠，药物与HIV蛋白酶的结合，以及 DNA的细沟，以及多肽和蛋白质与 膜的表面。总体策略是使用分子 动力学计算以产生稳定的构象，以评估 使用分子力学力场计算它们的气相能量，以及 使用连续介质溶剂模型计算溶剂化自由能。 气相和溶剂化自由能之和 构象自由能和结合自由能。该请求是为了 足够的计算机时间来执行特定的生产运行 利益问题。

The goal of the research described in this proposal is the calculation to conformational free energies and binding free energies relevant to the structure and function of biological macromolecules. The specific problems of interest include the indentification of stable protein folds, the binding of drugs to the HIV protease and to the minor groove of DNA, and the binding of peptides and proteins to the surface of membranes. The overall strategy is to use molecular dynamics calculations to generate stable conformations, to evaluate their gas phase energies using molecular mechanics force fields, and to evaluate solvation free energies using continuum solvent models. The sum of the gas phase and solvation free energies yield conformational and binding free energies. The request is for sufficient computer time to carry out production runs on the specific problems of interest.