PROTEIN-PROTEIN AND PROTEIN-DNA ASSOCIATION IN SOLUTION

描述：（改编自申请人摘要）拟议的研究将 发展和运用理论方法来研究蛋白质-蛋白质， 水介质中的蛋白质-DNA缔合现象，处理两者 平衡和动力学方面。 我们会特别注意 对关键的溶剂和电解质的影响， 生理水溶液中的大分子相互作用。 具体 项目包括：（一）蛋白质-蛋白质静电的研究 互动，制定和应用若干战略 这将允许快速计算精确的蛋白质-蛋白质（和 蛋白质-核酸）静电相互作用势 布朗动力学模拟和其他自动对接程序 需要从查找表中快速计算能量;（ii） 布朗动力学模拟方法的继续改进和检验 通过包含和评估有限的表面原子柔性， 快速计算静电力的经验方法。 （将应用于缔合和电子转移反应， 细胞色素和突变体，以进一步了解的作用， 对细胞色素电子转移的各种影响）; iii）模拟 基因组调节蛋白通过适应与DNA的非特异性结合 现有的布朗动力学方法来研究非特异性蛋白质-DNA 协会. cro阻遏物非特异性结合的动力学方面 蛋白质和E.大肠杆菌分解代谢物基因激活蛋白对B-DNA的作用， （四）开发软件，用于系统地搜索 蛋白质-蛋白质和蛋白质-DNA复合物的最佳对接构象， 允许对对接的构象异构体进行自动化的力引导的穷举搜索 这将避免在用户干预的情况下陷入局部能量最小值。

DESCRIPTION: (Adapted from Applicant's Abstract) The proposed study will develop and employ theoretical methods to investigate protein-protein and protein-DNA association phenomena in aqueous media, dealing with both equilibrium and dynamical aspects. Attention will be especially directed toward the crucial solvent and electrolyte effects which mediate macromolecular interactions in physiological aqueous solutions. Specific projects include: (i) A study of protein-protein electrostatic interactions, with the development and application of several strategies which will allow the rapid computation of accurate protein-protein (and protein-nucleic acid) electrostatic interaction potentials to benefit Brownian dynamics simulations and other automated docking procedures requiring rapid calculation of energies from look-up tables; (ii) The continued refinement and testing of the Brownian dynamics simulation method by the inclusion and evaluation of limited surface atom flexibility and empirical methods for rapid computation of electrostatic forces. (Application will be made to association and electron transfer reactions in the cytochromes and mutants to further our understanding of the role of a variety of influences on cytochrome electron transfer); iii) Simulation of nonspecific binding of genome regulatory proteins to DNA by an adaptation of existing Brownian dynamics methodology to study nonspecific protein-DNA associations. (Dynamical aspects of nonspecific binding of cro repressor protein and the E. coli catabolite gene activator protein to B-DNA will be studied); and iv) Development of software for systematic searching of optimum docking conformations of protein-protein and protein-DNA complexes, allowing an automated force-guided exhaustive search of docked conformers which would avoid trapping in local energy minima with user-intervention.