The use of high power THz radiation to probe low frequency protein vibrations that facilitate quantum tunnelling of hydrogen in enzyme systems

使用高功率太赫兹辐射探测低频蛋白质振动，促进酶系统中氢的量子隧道效应

• 批准号: EP/E016685/1
• 负责人: Peter Gardner
• 金额: $ 24.04万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FE016685%2F1
• 关键词: use; power; THz; radiation; probe

All of biology -- life itself -- depends on enzymes. Enzymes are large, natural molecules that allow specific biochemical reactions to take place quickly, that is to say enzymes are natural catalysts. They are very good catalysts, but as yet we do not understand what it is that makes them such good natural chemists. There are many reasons for studying enzymes and the reactions they catalyse: many drugs are enzyme inhibitors (they stop specific enzymes from working), so better understanding of enzymes will help in the design of new drugs. Better understanding of individual enzymes should also help understand and predict the effects of genetic variation, for example in understanding why some people may benefit from a particular drug, or may be at risk from a disease. Enzymes are also very good and environmentally catalysts - knowing how they function should help in the design and development of new 'green' catalysts for forensic, synthetic, analytical and biotechnological applications. Enzymes also show great promise as 'molecular machines' in the emerging field of nanotechnology. We will carry out a collaborative project based on experimental physics that supports existing research programmes at the international leading edge in providing a physical description of how enzymes work. We will focus on an enzyme whose reaction involves the transfer of hydrogen. Recent experimental work has shown that these reactions involve the quantum mechanical phenomenon of tunnelling, whereby hydrogen (because it is very light) is transferred from one molecule to another by going through the energy barrier, instead of over it. This might at first seem esoteric, but it seems that quantum tunnelling is essential in making enzyme reactions fast. Experimental results also suggest that the complex motions of large enzyme molecules may be crucial in helping tunnelling to happen within them. It seems that enzymes may have evolved specifically to make use of quantum tunnelling, and that this may be crucial in understanding how they function. Current computer modelling methods are very useful for studying aspects of enzyme reactions - making molecular 'movies' of how enzymes work - but modelling molecular motions in enzymes is particularly challenging. In this proposal, we will develop state-of-the-art methods based on emerging high power light sources to investigate the role of these motions in making enzymes work. The new methods we develop will pave the way for other researchers to also unravel the origin of the catalytic power of enzymes. The results should provide new and exciting insight into how enzymes function.

所有的生物--生命本身--都依赖于酶。酶是大的天然分子，可以使特定的生化反应快速发生，也就是说酶是天然催化剂。它们是非常好的催化剂，但我们至今还不明白是什么使它们成为如此好的天然化学家。研究酶及其催化的反应有很多原因：许多药物是酶抑制剂（它们阻止特定的酶工作），因此更好地了解酶将有助于新药的设计。更好地了解单个酶也应该有助于理解和预测遗传变异的影响，例如理解为什么有些人可能从某种特定药物中受益，或者可能有疾病的风险。酶也是非常好的环境催化剂-了解它们的功能有助于设计和开发用于法医、合成、分析和生物技术应用的新的“绿色”催化剂。酶在新兴的纳米技术领域也显示出作为“分子机器”的巨大潜力。我们将开展一个基于实验物理学的合作项目，支持国际领先的现有研究计划，提供酶如何工作的物理描述。我们将集中讨论一种酶，它的反应涉及氢的转移。最近的实验工作表明，这些反应涉及到量子力学的隧道效应，氢（因为它很轻）从一个分子转移到另一个分子是通过穿过能量势垒，而不是越过它，这可能看起来很深奥，但似乎量子隧道效应是使酶反应快速的关键。实验结果还表明，大酶分子的复杂运动可能是帮助隧道发生在它们内部的关键。看来酶可能已经进化到专门利用量子隧道效应，这可能是理解它们如何发挥作用的关键。目前的计算机建模方法对于研究酶反应的各个方面非常有用--制作酶如何工作的分子“电影”--但是对酶中的分子运动建模特别具有挑战性。在这项提案中，我们将开发基于新兴高功率光源的最先进的方法，以研究这些运动在使酶工作中的作用。我们开发的新方法将为其他研究人员揭开酶催化能力的起源铺平道路。这些结果应该为酶的功能提供新的和令人兴奋的见解。