Investigating the mechanism of proton translocation in solution: from small chemical systems to biomolecules

研究溶液中质子易位的机制：从小化学系统到生物分子

• 批准号: RGPIN-2017-06194
• 负责人: Iftimie, Radu
• 金额: $ 1.6万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=712082
• 关键词: Investigating; mechanism; proton; translocation; solution

The major theme of research outlined in this proposal is the investigation of the mechanism of proton transfer reactions in aqueous solutions using computational approaches. These processes play a fundamental role in numerous chemical and biochemical transformations, including acid-base reactions, enzyme catalysis, substrate binding and energy transduction. Theoretical investigations of proton transfer reactions in bulk water, at the interface between aqueous and hydrophobic media, as well as in biologically-relevant systems have been actively pursued for at least two decades. However, with the recent advent of ultrafast, time-resolved vibration spectroscopy techniques, the aforementioned proton transfer processes can for the first time be directly probed with the relevant space and time resolution. This opens new opportunities for computational chemistry to contribute to the advancement of our fundamental understanding of proton transfer reactions. A key objective of the present research program is to improve the existing arsenal of computational methods that can complement the aforementioned spectroscopy techniques. In this vein a novel methodology will be presented, which allows us to perform first-principles molecular dynamics calculations that can be related to a recently reported series of state-of-the-art, femtosecond-resolved UV pump/mid-IR probe acid-base neutralization experiments. An important goal of these theoretical studies will be to establish the elementary steps comprising acid-base neutralization in water, but the information thus obtained will also be relevant to processes at surfaces and interfaces. The investigation of proton translocation in the 3D H-bond network of bulk water will be complemented by a study of nuclear quantum effects. The latter project will involve adapting and developing existing computational methodologies that allow one to compute and interpret first-principles thermodynamic and kinetic isotope effects.

该提案中概述的研究的主要主题是使用计算方法研究水溶液中质子转移反应的机理。这些过程在许多化学和生化转化中起着基本作用，包括酸碱反应，酶催化，底物结合和能量转导。质子转移反应在大量水中的理论研究，在水性和疏水介质之间的界面以及生物学上与生物学相关的系统中的理论研究至少已被积极追求至少二十年。然而，随着最近超快，时间分辨振动光谱技术的出现，上述质子转移过程可以首次通过相关的空间和时间分辨率直接探测。这为计算化学的新机会开辟了新的机会，从而有助于我们对质子转移反应的基本理解的发展。 本研究计划的一个关键目的是改善可以补充上述光谱技术的计算方法的现有库。在这种情况下，将提出一种新颖的方法，这使我们能够执行第一原理分子动力学计算，该计算可能与最近报道的一系列最新的，飞秒的紫外线泵/中IIR探针酸有关 - 基本中和实验。这些理论研究的一个重要目标是建立包含水中酸碱中和的基本步骤，但是因此获得的信息也将与表面和接口处的过程有关。 核量子效应的研究将补充3D H键网络中质子易位的研究。后一个项目将涉及适应和开发现有的计算方法，这些方法允许人们计算和解释第一原理热力学和动力学同位素效应。