权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Catalysis in motion: accessing how fast motions facilitate catalysis through pump-probe and fast time resolved spectroscopies.

运动中的催化：通过泵浦探针和快速时间分辨光谱了解运动促进催化的速度。

基本信息

批准号：
EP/J020192/1
负责人：
Nigel Scrutton
金额：
$ 135.08万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FJ020192%2F1
关键词：
Catalysis motion accessing how fast

项目摘要

The precise origin(s) of the catalytic power of enzymes remains an unresolved problem that hampers their exploitation in meeting contemporary challenges in, for example, chemicals and materials manufacture, the energy agenda and healthcare. While the role of electrostatic contributions, hydrogen bonding and desolvation to transition state stabilisation (and thus catalysis) have been long recognised as playing an important role, the involvement and contribution of dynamical effects - atomic motions across wide ranging timescales, from seconds to femtoseconds - remains controversial. Of particular note has been recent discussion of the direct coupling of dynamical effects (vibrations/motions) to the chemical (reaction) coordinate (i.e. to the making and breaking of bonds), and whether this enhances the rate of enzymatic reactions. In this application the focus is on fast motions at the femtosecond to picosecond timescale and the possible coupling of such motions to the chemical reaction coordinate. The purpose is to explore their potential contribution to both the catalytic effect on, and the observed rate of, the intrinsic chemical step, the models developed to account for their effect, and the experimental and theoretical studies that support the existence of such motions. The potential importance of these motions has largely arisen from studies of quantum mechanical tunnelling of hydrogen in enzyme systems, but is equally relevant to classical (over-the-barrier) reactions. The challenge is to develop atomistic understanding of such motions and develop more comprehensive models of enzyme catalysis that explicitly recognise the potential importance of fast dynamics in reaction barrier crossing. These aims and challenges will be addressed in an innovative programme integrating new capabilities in femtosecond spectroscopy with allied spectroscopy capabilities, isotope effect analysis and studies of model enzyme catalysts that are activated either thermally or by light.This is a truly cross disciplinary programme requiring expertise in ultrafast laser spectroscopy, physical chemistry, structural science, computation and modelling/theory. The applicant has assembled a unique team of experts across these disciplines based at the University of Manchester and the Harwell Research Complex. He has established leading capabilities in ultrafast spectrocopy and allied areas at Manchester and contributed to the development and use of new capabilities at Rutherford Appleton Laboratory in femtosecond IR spectroscopy. This combines to place the applicant in field-leading position and secure for the UK unique capabilities that will elucidate the role of fast dynamics in enzyme systems. The work addresses a major and controversial hypothesis in contemporary catalysis research which goes to the very heart of catalysis mechanisms. This will lead to more comprehensive understanding of bio-catalysis that will guide the predictive design of enzyme systems for use in synthetic biology and industrial applications, which is crucial to the emerging white (industrial) biotechnology economy.

酶催化能力的确切来源仍然是一个未解决的问题，阻碍了酶的利用以应对当代挑战，例如化学品和材料制造、能源议程和医疗保健。虽然静电贡献、氢键和去溶剂化对过渡态稳定（以及催化）的作用长期以来一直被认为发挥着重要作用，但动力学效应（从秒到飞秒的广泛时间尺度上的原子运动）的参与和贡献仍然存在争议。特别值得注意的是最近关于动态效应（振动/运动）与化学（反应）坐标（即键的形成和断裂）的直接耦合的讨论，以及这是否会提高酶促反应的速率。在此应用中，重点是飞秒到皮秒时间尺度的快速运动以及此类运动与化学反应坐标的可能耦合。目的是探索它们对内在化学步骤的催化效应和观察到的速率的潜在贡献，为解释其效应而开发的模型，以及支持此类运动存在的实验和理论研究。这些运动的潜在重要性很大程度上源于对酶系统中氢的量子力学隧道效应的研究，但同样与经典（越障）反应相关。面临的挑战是发展对此类运动的原子理解，并开发更全面的酶催化模型，明确认识到快速动力学在反应障碍跨越中的潜在重要性。这些目申请人在曼彻斯特大学和哈韦尔研究中心组建了一支由这些学科的独特专家组成的团队。他在曼彻斯特建立了超快光谱学和相关领域的领先能力，并为卢瑟福阿普尔顿实验室飞秒红外光谱新功能的开发和使用做出了贡献。这结合起来使申请人处于该领域的领先地位，并确保英国独特的能力，这将阐明快速动力学在酶系统中的作用。这项工作提出了当代催化研究中一个重要且有争议的假设，该假设涉及催化机制的核心。这将导致对生物催化的更全面的理解，从而指导用于合成生物学和工业应用的酶系统的预测设计，这对于新兴的白色（工业）生物技术经济至关重要。