Quantum Mechanical/Molecular Mechanical Study of the Search Strategy and Catalytic Mechanism of the DNA Repair Enzyme, MutY

DNA修复酶MutY的搜索策略和催化机制的量子力学/分子力学研究

• 批准号: 0502600
• 负责人: Jeremy Arey
• 金额: $ 11.69万
• 依托单位: Arey Jeremy S
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2007-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0502600&HistoricalAwards=false
• 关键词: Quantum; Mechanical; Molecular; Study; Search

The MPS Distinguished International Postdoctoral Fellowship Program (MPS-DRF) enables U.S. scientists to conduct research abroad. The fellowship allows awardees to establish long-term international collaborations that will benefit them and the U.S. scientific community by developing international connections and perspectives in future science leaders.This award will support a 24-month research fellowship for Dr. Jeremy S. Arey to work with Professor Ursula Rothlisberger and her group at the Laboratory of Computational Chemistry and Biochemistry, Federal Institute of Technology, Lausanne, Switzerland. The proposed work will attempt to resolve the mechanisms governing: (1) the MutY search for DNA lesion sites; (2) MutY recognition of and binding to lesion sites; (3) the catalytic adenine cleavage by MutY; and (4) the MutY release step. These problems will be addressed using mixed quantum mechanical/molecular mechanical molecular dynamics simulations, applying enhanced sampling techniques to treat processes for long time scales (minutes to hours).Professor Rothlisberger is a leader in this area of research and has an international reputation in the sub-field of quantum mechanical/molecular mechanical (QM/MM) molecular dynamics. Prof. Rothlisberger's Lausanne Laboratory, with 7 postdoctoral students and 9 Ph.D. students currently in her research group, are ideally set up to provide superb facilities and good opportunities for collaboration. This broadening experience will provide Dr. Arey with a strong foundation to return to the U.S. to pursue his plans for an academic career in a research area of growing importance.

MPS杰出国际博士后奖学金计划（MPS-DRF）使美国科学家能够在国外进行研究。该奖学金允许获奖者建立长期的国际合作，这将有利于他们和美国科学界通过发展国际联系和未来的科学领导者的观点。Arey与瑞士洛桑联邦理工学院计算化学和生物化学实验室的Ursula Rothlisberger教授及其小组合作。拟开展的工作将试图解决以下机制：（1）MutY寻找DNA损伤位点;（2）MutY识别并结合损伤位点;（3）MutY催化腺嘌呤切割;（4）MutY释放步骤。这些问题将使用混合量子力学/分子力学分子动力学模拟，应用增强的采样技术来处理长时间尺度（分钟到小时）的过程来解决。Rothlisberger教授是这一研究领域的领导者，在量子力学/分子力学（QM/MM）分子动力学子领域享有国际声誉。Rothlisberger教授的洛桑实验室，拥有7名博士后和9名博士。目前在她的研究小组的学生，是理想的设置，提供一流的设施和良好的合作机会。这一不断扩大的经验将为Arey博士提供一个坚实的基础，使他能够回到美国，在一个日益重要的研究领域继续他的学术生涯。