THEORY OF BIOMOLECULAR DIFFUSION

描述：（改编自申请人摘要）。 本研究是 旨在增加我们对扩散控制过程的理解， 生物学 更准确地说，理论和计算工作将完成 提供越来越详细和准确的分析率， 扩散控制的酶促反应。 一些选定的生物分子 系统将进行深入研究。 这种做法应有助于 发现具有广泛相关性的概念， 选择用于研究的特定系统的机制。 比较将 在各种条件下获得的实验数据， 测试理论模型，并帮助解释 实验 拟议工作的其他部分涉及制定 用于扩散模拟的工具，其次是用于计算 静电力，这是特别重要的影响， 生物分子扩散 本项目将寻求回答的具体问题包括： 以下. 不同部位的改造效果如何联合收割机 产生Cu、Zn超氧化物歧化酶催化速率的变化 (SOD)? 如何模拟衬底的扩散遇到 SOD的表面与随后的详细模拟相结合， 事件，以提供更完整的描述SOD活性？ 能否 在这项工作中开发的工具可以扩展到酶，如锰SOD和 磷酸丙糖异构酶（TIM），其中连续较大的运动， 酶可以调节底物进入活性位点？ 这项工作的健康相关性在于它应该产生的工具， 具有所需动力学性质的分子的合理设计。 例如，SOD是 正在考虑用于药理学用途;这项工作中开发的方法 可以帮助工程SOD增加其扩散控制率， 行动上

DESCRIPTION: (Adapted from Applicant's Abstract). This research is intended to increase our understanding of diffusion-controlled processes in biology. More precisely, theoretical and computational work will be done to provide increasingly detailed and accurate analyses of the rates of diffusion-controlled enzymatic reactions. A few selected biomolecular systems will be studied in great depth. This approach should facilitate the discovery of concepts of broad relevance in addition to clarifying the mechanisms of the particular systems chosen for study. Comparisons will be made to experimental data obtained under a variety of conditions, both to test the theoretical models and to aid in the interpretation of the experiments. Other parts of the proposed work involve the development of tools for diffusional simulations and, secondarily, for the calculation of electrostatic forces, which are of special importance in influencing biomolecular diffusion. Among the specific questions that this project will seek to answer are the following. How do the effects of modifications at different sites combine to produce changes in the catalytic rate of Cu, Zn superoxide dismutase (SOD)? How can simulations of the diffusional encounter of substrate with the surface of SOD be combined with detailed simulations of subsequent events to provide a more complete description of SOD activity? Can the tools developed in this work be extended to enzymes such as Mn SOD and triose phosphate isomerase (TIM), where successively larger motions in the enzyme may modulate substrate access to the active site? The health relatedness of this work is in the tools it should yield for the rational design of molecules with desired kinetic properties. E.G., SOD is being considered for pharmacologic use; the methods developed in this work could help in engineering SOD to increase its diffusion-controlled rate of action.