Quantum Nuclear Dynamics and Enzyme Chemistry

描述（由申请人提供）：对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括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括量子效应的方法还远没有发展得那么好。此外，需要发现关于生化反应机制的原子细节，而不需要预先设想的反应机制。本申请中描述的程序旨在开发和应用满足这些需求的方法。我们将实现一种新的方法，结合质心量子动力学与过渡路径采样，包括生物化学中的量子效应。如果时间允许， 应用该方法对酵母醇脱氢酶催化反应中核量子效应的重要性进行了定量分析。为了做到这一点，我们将研究以下3个具体目标：具体目标1：我们将开发和应用一种方法，将量子动力学纳入过渡路径采样（TPS）的框架内。具体目标2开发并应用受量子动力学影响的反应机理的计算方法，以及包括和不包括量子动力学影响的酶催化反应的化学步骤的计算方法。具体目标3：我们将应用特定目标1和2中开发的方法研究酵母醇脱氢酶（YADH）催化的反应。

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.)