Novel methodologies for conformational sampling and QM/MM simulations in complex systems

复杂系统中构象采样和 QM/MM 模拟的新方法

• 批准号: 0704036
• 负责人: Mark Tuckerman
• 金额: $ 42.75万
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0704036&HistoricalAwards=false
• 关键词: Novel; methodologies; conformational; sampling; QM

Mark E. Tuckerman of New York University is supported by the Theoretical and Computational Chemistry program to develop and implement methods based on specialized variable transformations that are capable of sampling the conformational equilibria of complex systems. This approach reduces the effects of energy barriers without altering thermodynamic and equilibrium properties. Applications of these methods include small peptides as test cases, and fast-folding proteins. A second theme of the research is to develop pseudopotentials appropriate for use in quantum mechanical/molecular mechanical (QM/MM) methods. An initial application of this method is to study the catalytic mechanism of the enzyme histone deacetylase, which is linked to various types of cancer. This work is having a broad impact in developing sampling and search algorithms for bio-simulations. Codes developed in this research, as well as a database of pseudopotentials, are freely available on the PI''s web site. Research results are incorporated into the classroom at the undergraduate and graduate level. Outreach to the community includes non-technical talks to students and faculty at regional middle schools, high school, colleges and universities.

Mark E.纽约大学的塔克曼得到了理论和计算化学项目的支持，以开发和实施基于专门变量变换的方法，这些方法能够对复杂系统的构象平衡进行采样。 这种方法在不改变热力学和平衡性质的情况下减少了能量势垒的影响。 这些方法的应用包括作为测试案例的小肽和快速折叠蛋白质。 研究的第二个主题是开发适用于量子力学/分子力学（QM/MM）方法的赝势。 这种方法的最初应用是研究组蛋白脱乙酰酶的催化机制，该酶与各种类型的癌症有关。 这项工作在开发生物模拟的采样和搜索算法方面产生了广泛的影响。 在这项研究中开发的代码，以及赝势数据库，可以在PI的网站上免费获得。 研究成果被纳入本科和研究生阶段的课堂。 对社区的宣传包括与地区中学、高中、学院和大学的学生和教师进行非技术性会谈。