Achieving Long Timescale Sampling in Biomolecular Simulations

在生物分子模拟中实现长时间尺度采样

• 批准号: 1158284
• 负责人: Wei Yang
• 金额: $ 63.3万
• 依托单位: Florida State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1158284&HistoricalAwards=false
• 关键词: Achieving; Long; Timescale; Sampling; Biomolecular; Achieving; Long; Timescale; Sampling; Biomolecular

Abstract:Scientific merit: Long timescale conformational fluctuations can be responsible for unusual protein electrostatic effects and remote modulation of enzymatic reactions. Due to the timescale limitation, accurate understanding of these events via computer simulation has been very challenging. The goal of this research is to develop and apply novel molecular dynamics simulation methods to quantitatively describe complex biomolecular phenomena that usually occur in much longer timescales than what conventional techniques can achieve. In this project, specialized computer simulation algorithms will be developed and employed to enhance the sampling power of biomolecular simulations. Specifically, the main objectives will be accomplished in two focused areas: (1) Quantitative prediction of protein electrostatic effects and understanding their coupling with protein conformational transitions; (2) Understanding how slow enzyme fluctuations prepare unique catalytic environments to activate chemical reactions. These studies will provide deeper understanding of the roles that protein conformational changes play in key biological processes.Broader impacts: The computer simulation methods under development will be distributed to general scientific community. Some specific algorithms will very possibly become major techniques in related research areas. The success of this research will motivate more problem-oriented sampling design efforts in the field of biomolecular simulation. Synergistic with the scientific project, a special graduate course "Time-scale and Length-scale in Biology" will be further developed. National and international meetings and workshops will continue to be organized by the author to motivate and catalyze the education of younger-generation scientists on the subject of quantitative computational biophysics. Efforts will continue in the involvement of undergraduate students and high school students in this research, using computer simulations to explore protein structures, dynamics, and functions.

摘要：科学优点：长时间构象波动可能导致异常的蛋白质静电作用和酶促反应的远程调节。由于时间尺度的限制，通过计算机模拟对这些事件的准确理解非常具有挑战性。这项研究的目的是开发和应用新颖的分子动力学仿真方法来定量描述通常在时间尺度上比常规技术实现的时间更长的时间表。在该项目中，将开发和使用专门的计算机模拟算法来增强生物分子模拟的采样能力。具体而言，主要目标将在两个集中的领域实现：（1）蛋白质静电效应的定量预测并理解其与蛋白质构象转变的耦合； （2）了解酶波动慢的速度如何准备独特的催化环境以激活化学反应。这些研究将对蛋白质构象变化在关键生物学过程中发挥作用的作用有更深入的了解。Boader的影响：正在开发的计算机仿真方法将分配给一般科学界。一些特定的算法很可能成为相关研究领域的主要技术。这项研究的成功将激发更多面向问题的采样设计在生物分子模拟领域。与科学项目协同作用，特殊的研究生课程“生物学的时间尺度和长度尺度”将进一步发展。 作者将继续组织国家和国际会议和研讨会，以激励和催化年轻代科学家就定量计算生物物理学的主题进行教育。在本科生和高中生参与这项研究的过程中，将继续努力，使用计算机模拟来探索蛋白质结构，动态和功能。