PROTEIN-PROTEIN AND PROTEIN-DNA ASSOCIATION IN SOLUTION

描述：(改编自申请者摘要)拟议的研究将 开发和使用理论方法来研究蛋白质-蛋白质和 水介质中的蛋白质-DNA结合现象，处理两者 平衡和动力方面。我们会特别注意 对于关键的溶剂和电解液的影响 生理水溶液中的大分子相互作用。特定的 项目包括：(I)蛋白质-蛋白质静电研究 与若干战略的发展和应用相互作用 这将允许快速计算准确的蛋白质-蛋白质(和 蛋白质-核酸)静电相互作用势有利 布朗动力学模拟和其他自动对接过程 需要从查找表快速计算能量； 布朗动力学模拟方法的进一步改进和检验 通过纳入和评估有限的表面原子柔性和 静电力快速计算的经验方法。 (将应用于缔合和电子转移反应 细胞色素和突变体进一步加深了我们对A 对细胞色素电子转移的各种影响)；iii)模拟 通过修饰实现基因组调节蛋白与DNA的非特异性结合 现有布朗动力学方法研究非特异性蛋白质-DNA 联想。(CRO抑制物非特异性结合的动力学方面 蛋白和大肠杆菌分解代谢基因激活剂蛋白将B-DNA 研究)；以及iv)开发系统搜索的软件 蛋白质-蛋白质和蛋白质-DNA复合体的最佳对接构象， 允许对停靠的构象进行自动力引导穷尽搜索 这将避免在用户干预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.