Quantum Nuclear Dynamics and Enzyme Chemistry

描述（申请人提供）：核运动的量子效应可能在某些酶催化反应中起重要作用。虽然在生物系统的电子分布中包含量子力学的方法现在已经成熟（例如QM/MM方法），但在原子核动力学中包含量子效应的方法还远远没有发展好。此外，有必要发现有关生化反应机制的原子细节，而不需要先入为主的反应机制。本应用程序中描述的程序旨在开发和应用满足这些需求的方法。我们将实现一种结合质心量子动力学和跃迁路径采样的新方法，以包括生物化学中的量子效应。如果时间允许，我们会的

DESCRIPTION (provided by applicant): Quantum effects on nuclear motion may play an important role in certain enzymatically- catalyzed reactions. While methods to include quantum mechanics in electron distributions for biological systems are now mature (for example QM/MM methods) methods to include quantum effects on the dynamics of nuclei are far less well developed. In addition, there is a need to discover atomic details regarding the mechanism of biochemical reactions with no need for preconceived reaction mechanism. The program described in this application is designed to develop and apply methods that answer these needs. We will implement a new method that combines centroid quantum dynamics with transition path sampling to include quantum effects in biological chemistry. If time allows we will apply the method to quantify the importance of nuclear quantum effects in the reaction catalyzed by yeast alcohol dehydrogenase. In order to do this we will study the following 3 specific aims: Specific Aim 1: We will develop and apply a method to include quantum dynamics within the framework of Transition Path Sampling (TPS.) Specific Aim 2 We will develop and apply methods to calculate the reaction mechanism as affected by quantum dynamics, and also to calculate the rates of the chemical step of enzymatically catalyzed reactions including and excluding quantum dynamic effects. Specific Aim 3: We will apply the methods developed in Specific Aims 1 and 2 to the study of the reaction catalyzed by yeast alcohol dehydrogenase (YADH.)