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）得到了化学分部的理论模型和计算方法计划的奖励，以进行研究，开发和应用新颖方法，以增强构象采样，自由能预测以及混合QM/MM计算。该项目的目的是根据建模和模拟以新颖的方式解决在凝结阶段中直接测量的复杂化学过程的可直接测量的结构和动力学量。为此，正在开发一种基于引入专业变量转换函数中的专门变量转换的新型方法。这种方法在不改变系统的热力学和平衡特性的情况下降低了能屏障的影响。应用包括从肽到快速折叠蛋白的复杂性越来越高的系统。因此，从人类健康（蛋白质折叠和折叠式折叠的模拟）到新型材料的合理设计等领域有潜在的好处。 该项目的第二部分通过量子机械/分子机械（QM/mm）方法解决了大型生物分子（例如酶）中的化学反应性。开发了一种严格的分子伪潜能理论，用于描述QM和MM子系统之间的相互作用。新的伪潜电将在获奖者网站上提供给社区的数据库中。方法论开发及其将其纳入社区可自由使用的用户友好开源软件是该项目的组成部分，这些软件强烈影响计算化学和生物学，从而导致了解决硅中复杂问题的新方法。塔克曼（Tuckerman）的本科生，研究生和博士后研究人员是一个多样化和性别平衡的群体。目前可以通过网络获得的研究生统计力学课程的笔记补充了该项目的进步。美国数学协会的数学发言人局（MSB）的宣传研讨会丰富了区域中学，高中，高中，学院和大学的背景，这些主题超出了传统的数学课程。