Quantum Nuclear Dynamics and Enzyme Chemistry

描述(申请人提供)：原子核运动的量子效应可能在某些酶催化的反应中发挥重要作用。虽然将量子力学包含在生物系统的电子分布中的方法现在已经成熟(例如QM/MM方法)，但将量子效应包含在原子核动力学中的方法还远远不够成熟。此外，有必要发现有关生化反应机理的原子细节，而不需要预先设想的反应机理。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。我们将实施一种新的方法，将质心量子动力学与跃迁路径采样相结合，将量子效应纳入生物化学。如果时间允许，我们将 应用该方法量化了核量子效应在酵母醇脱氢酶催化反应中的重要性。为此，我们将研究以下三个具体目标：具体目标1：我们将开发和应用一种方法，将量子动力学包括在跃迁路径采样(TPS)的框架内。具体目标2我们将开发和应用各种方法来计算受量子动力学影响的反应机理，并计算包括和排除量子动力学影响的酶催化反应的化学步骤的速率。具体目标3：我们将应用在具体目标1和2中开发的方法来研究酵母醇脱氢酶(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.)