Linking experiment to theory: Quantum entanglement during enzyme catalysis

物理学家通常用两种不同的模型来描述他们周围的世界：经典牛顿力学和量子力学。虽然牛顿发展了他的理论来描述行星的运动，但量子力学由于其更大的复杂性，通常只用于描述由几个原子或更少原子组成的系统。尽管如此，量子力学仍然是一个令人兴奋的研究领域，它的应用导致了最近在隐形传态和信息理论方面的突破。生物学家经常忽略量子力学，然而现在越来越明显的是，量子力学隧道效应在简单的生物电子和氢转移反应中起着重要作用。在这些反应中，转移的电子或氢的波/粒子二象性允许其位置变得离域（在空间上涂抹），从而影响反应进行的方式。量子力学的一个更奇怪的结果是叠加和纠缠，两个或两个以上遥远物体的量子态是联系在一起的。拟议的研究旨在利用我们在研究电子和氢隧穿反应时开发的方法来确定其他量子力学现象是否影响生物过程。具体来说，这项研究旨在寻找不同底物分子在酶（如DNA聚合酶）活性位点纠缠的证据——这是最近从量子搜索算法研究中出现的一个想法。DNA——“生命分子”——是由四种不同的核苷酸单体（dNTPs）组成的聚合物，分别表示为a、T、C和g。DNA复制是生物体在细胞分裂前复制DNA的方法，是生物遗传的基础。在复制过程中，双链DNA螺旋的每一条链都可以作为另一条DNA链复制的模板。这种复制是由DNA聚合酶催化的，这种酶一旦结合到单链DNA模板上，就会沿着模板链移动，一次一个地添加所需的dNTP，从而产生双链DNA。由于一次只能结合一个dNTP底物，因此DNA聚合酶在每一步复制过程中需要四次尝试才能找到正确的dNTP （a、T、C或G）。然而，在量子力学的世界里，理论上两个或两个以上的dNTPs可能会纠缠在一起，同时在DNA聚合酶的活性位点上叠加。如果是这样的话，酶就可以预先选择正确的底物，而不必盲目地寻找正确的dNTP。本研究旨在结合实验酶学和计算/理论化学来确定这种底物纠缠是否可能。这种方法可以扩展到研究许多其他生物学上重要的酶，这些酶作用于多种底物。此外，由于突变是由DNA聚合酶偶尔不忠导致的DNA复制错误引起的，因此更深入地了解这种酶如何区分其四种dNTP底物可能会导致衰老和癌症的预防性治疗。此外，如果量子纠缠在催化过程中起着可观察到的作用，这将证明相干量子态可以具有“有用的”寿命——这是理论物理学中的一个重要问题，特别是在新兴的量子计算领域。

Physicists generally describe the world around them using one of two different models: classical Newtonian mechanics and quantum mechanics. While Newton developed his theory to describe the motion of the planets, quantum mechanics, due to it's greater complexity, is typically only used to describe systems of a few atoms or less. Despite this, quantum mechanics remains an exciting area of research, with its application leading to recent breakthroughs in teleportation and information theory. Biologists have often ignored quantum mechanics, yet it is now becoming evident that quantum mechanical tunnelling plays a significant role during simple biological electron and hydrogen transfer reactions. During these reactions, the wave/particle duality of the transferred electron or hydrogen allows its position to become delocalised (smeared out over space), thus affecting the way the reaction proceeds. An even stranger consequence of quantum mechanics is superposition and entanglement, where the quantum states of two or more distant objects are linked. The proposed research aims to utilise methods we have developed while investigating electron and hydrogen tunnelling reactions to determine whether other quantum mechanical phenomena influence biology processes. Specifically, this research aims to look for evidence of entanglement of different substrate molecules in the active sites of enzymes such as DNA polymerase - an idea that has recently emerged from studies of quantum search algorithms. DNA - 'the molecule of life' - is a polymer of four different nucleotide monomers (dNTPs), denoted A, T, C and G. DNA replication, the method by which living organisms copy their DNA prior to cell division, is the basis for biological inheritance. During replication, each strand of the double-stranded DNA helix can act as a template for the reproduction of another strand of DNA. This replication is catalysed by DNA polymerase, an enzyme that once bound to a section of single stranded DNA template, produces double-stranded DNA by moving along the template strand adding the required dNTP, one at a time. As only one dNTP substrate can bind at a time, it should take four attempts for DNA polymerase to find the correct dNTP (A, T, C or G) during each step of replication. However, in a quantum mechanical world, it is theoretically possible that two or more dNTPs could become entangled and simultaneously superimposed within the active site of DNA polymerase. If this is the case, the enzyme could pre-select the correct substrate without having to perform a blind search for the correct dNTP. This research aims to use a combination of experimental enzymology and computational/theoretical chemistry to determine whether such an entanglement of substrates is possible. This approach can then be extended to investigate many other biologically important enzymes that act on multiple substrates. Further, as mutations are caused by errors in DNA replication due to occasional DNA polymerase infidelity, a greater understanding of how this enzyme distinguishes between its four dNTP substrates could lead to preventative treatments of aging and cancer. Additionally, if quantum entanglement plays an observable role during catalysis, this would demonstrate that coherent quantum states can have 'useful' lifetimes - an important question in theoretical physics and particularly in the emerging field of quantum computing.