Quantum Nuclear Dynamics and Enzyme Chemistry

量子核动力学和酶化学

• 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
• 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

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）：量子对核运动的影响可能在某些酶上催化反应中起重要作用。现在，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）方法，包括对核动力学的量子效应的发展远不足以发达。此外，有必要发现有关生化反应机制的原子细节，而无需先天的反应机理。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。我们将实施一种新方法，将质心量子动力学与过渡路径采样相结合，以在生物学中包括量子效应。如果时间允许，我们将 应用该方法来量化核量子作用在由酵母醇脱氢酶催化的反应中的重要性。为此，我们将研究以下3个特定目的：具体目的1：我们将开发并应用一种方法，将量子动态包括在过渡路径采样框架内（TPS。）具体目的2我们将开发和应用方法来计算受量子动态影响的反应机制，并计算出量子型量子的化学速率，包括量子量的量子量和排除反应的化学速率。特定目标3：我们将在特定目标1和2中使用的方法应用于酵母醇脱氢酶催化的反应（YADH。）的研究。