Quantum Nuclear Dynamics and Enzyme Chemistry

量子核动力学和酶化学

基本信息

批准号：
8636569
负责人：
STEVEN D SCHWARTZ
金额：
$ 18.24万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8636569
关键词：
Quantum Nuclear Dynamics Enzyme Chemistry

项目摘要

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.)

描述（由申请人提供）：核运动的量子效应可能在某些酶催化反应中发挥重要作用。虽然将量子力学纳入生物系统电子分布的方法现已成熟（例如 QM/MM 方法），但将量子效应纳入原子核动力学的方法还远未开发成熟。此外，需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。我们将实施一种将质心量子动力学与跃迁路径采样相结合的新方法，以将量子效应纳入生物化学中。如果时间允许我们会应用该方法量化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 3 个具体目标：具体目标 1：我们将开发并应用一种方法，将量子动力学纳入过渡路径采样 (TPS) 的框架内。具体目标 2 我们将开发并应用方法计算受量子动力学影响的反应机理，并计算酶催化反应的化学步骤的速率，包括和排除量子动力学效应。具体目标3：我们将应用具体目标1和2中开发的方法来研究酵母乙醇脱氢酶（YADH）催化的反应。