Development and application of novel methods for enhanced conformational sampling, free energy prediction, and hybrid QM/MM calculations

增强构象采样、自由能预测和混合 QM/MM 计算新方法的开发和应用

• 批准号: 1012545
• 负责人: Mark Tuckerman
• 金额: $ 43.5万
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1012545&HistoricalAwards=false
• 关键词: Development; application; novel; methods; enhanced

Mark Tuckerman of New York University is supported by an award from the Theory Models and Computational Method program of the Chemistry Division to carry out research, development, and application of novel methods for enhanced conformational sampling, free energy prediction, and hybrid QM/MM calculations. The aim of this project is to address directly measurable structural and dynamical quantities of complex chemical processes in the condensed phase in novel ways based on modeling and simulation. To that end, a novel approach to conformational sampling based on the introduction of specialized variable transformations in the classical canonical partition function is being developed. This approach reduces the effect of energy barriers without altering thermodynamic and equilibrium properties of the system. Applications include systems with increasing complexity, from peptides to fast-folding proteins. Hence, there are potential benefits to fields ranging from human health (simulations of protein folding and miss-folding) to the rational design of novel materials. A second component of the project addresses chemical reactivity in large biomolecules such as enzymes via the quantum mechanical/molecular mechanical (QM/MM) method. A rigorous theory of molecular pseudo-potentials is developed for describing the interaction between the QM and MM subsystems. The new pseudo-potentials are to be gathered in a database made available to the community on the awardee's Web site. Methodology development and its incorporation into user-friendly open-source software that is freely available to the community are components of the project that strongly impact computational chemistry and biology, leading to new approaches for solving complex problems in silico. Tuckerman's undergraduate and graduate students and postdoctoral researchers are a diverse and gender-balanced group. Notes of the graduate Statistical Mechanics course, currently available through the Web, are supplemented with advances in this project. Outreach seminars at the Mathematics Speakers Bureau (MSB) of the New York section of the Mathematical Association of America enrich the background of students and faculty of regional middle schools, high schools, colleges and universities on topics reaching beyond the traditional math curriculum.

纽约大学的马克·塔克曼 (Mark Tuckerman) 获得化学系理论模型和计算方法项目的资助，开展增强构象采样、自由能预测和混合 QM/MM 计算的新方法的研究、开发和应用。该项目的目的是基于建模和模拟，以新颖的方式解决凝聚相中复杂化学过程的可直接测量的结构和动力学量。为此，正在开发一种新的构象采样方法，该方法基于在经典规范配分函数中引入专门的变量变换。这种方法减少了能垒的影响，而不改变系统的热力学和平衡特性。应用包括复杂性不断增加的系统，从肽到快速折叠蛋白质。因此，从人类健康（蛋白质折叠和错误折叠的模拟）到新型材料的合理设计等领域都有潜在的好处。 该项目的第二个组成部分通过量子力学/分子力学（QM/MM）方法解决酶等大型生物分子的化学反应性。发展了严格的分子赝势理论来描述 QM 和 MM 子系统之间的相互作用。新的赝势将被收集到数据库中，并在获奖者的网站上向社区提供。方法开发及其纳入社区免费提供的用户友好开源软件是该项目的组成部分，对计算化学和生物学产生了强烈影响，从而产生了在计算机中解决复杂问题的新方法。塔克曼的本科生、研究生以及博士后研究人员是一个多元化且性别平衡的群体。目前可通过网络获取研究生统计力学课程的笔记，并通过该项目的进展进行补充。美国数学协会纽约分部数学演讲局 (MSB) 举办的外展研讨会丰富了地区初中、高中、学院和大学学生和教师的背景知识，主题超出了传统数学课程的范围。