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

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开展研究。该奖学金允许获奖者建立长期的国际合作，通过发展未来科学领袖的国际联系和视角，使他们和美国科学界受益。该奖项将支持Jeremy S.Arey博士与Ursula Rothlisberger教授和她的团队在瑞士洛桑联邦理工学院计算化学和生物化学实验室工作的24个月研究奖学金。这项拟议的工作将试图解决以下机制：(1)MutY寻找DNA损伤部位；(2)MutY识别和结合病变部位；(3)MutY催化腺嘌呤裂解；(4)MutY释放步骤。这些问题将通过混合量子力学/分子力学分子动力学模拟来解决，应用增强的采样技术来处理长时间尺度(几分钟到几小时)的过程。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)分子动力学的子领域拥有国际声誉。Rothlisberger教授的洛桑实验室目前有7名博士后和9名博士后，她的研究小组是为提供一流的设施和良好的合作机会而建立的理想实验室。这种不断扩大的经验将为艾瑞博士回到美国，在一个日益重要的研究领域追求他的学术生涯计划提供坚实的基础。

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.