Physics of Life - Noise, Information and Evolution in Protein Binding

秩序是如何从混乱中走出来的？仿佛复杂的“生命奇迹”还不足以让我们感到惊讶，有关信息和能量如何在活的细胞和有机体中流动的分子故事讲述了一个更奇怪的故事。因为在生命的分子构建块的维度上--完美折叠成功能形式的长蛋白质分子，编码其生物体结构的更长的DNA，以及组织细胞与周围环境之间生化交通的细胞膜--所有这些都受到持续、快速的随机波动的影响。起初，每一个组件的热碰撞似乎都是为了对抗作为生命出现迹象的秩序和结构的出现。然而，最近物理学家和生物学家之间的跨学科合作已经开始发现，生命已经进化到与噪音波动合作而不是对抗噪音的深度。这个项目将花费5年的时间进行集中研究，详细探索随机和噪音在生物学中被招募的三种基本方式，将拟议的研究员、两名博士后研究员和广泛的合作者的经验带到一起。第一个例子就是细胞中信息处理的核心。“异构体”是蛋白质分子与另一个分子(无论是较小的物种，还是像DNA这样的大分子)结合的效果，当且仅当第二个“信号”分子也在不同的位置与它结合时。信号分子的存在可以在另一个结合部位“远处”感觉到。我们将开发理论和计算工具来探索热涨落的背景如何可以用来携带信号，并从生物学中学习波动弹性物质的物理学。第二个例子继续蛋白质结合的主题，但现在到其他蛋白质。当我们发现蜘蛛丝和蚕丝的优异性能时，我们会发现这些纤维是如何在自然界中形成的。不知何故，在合适的流动条件下(在喷丝板上)，丝蛋白的分子粘性恰好足以触发它们组装成纤维。我们将与实验同事密切合作，发展流动组装理论，以帮助找出是什么让丝绸及其加工如此引人注目。第三项工作采用了随机运动的概念，但现在是在更高的进化本身水平上。寻找提供信号和丝素结合特性的蛋白质结构，是在生物体基因组编码的可能性的难以想象的广阔空间中进行的。这个空间中的随机跳跃，就像蛋白质本身的随机运动一样，以某种方式用来寻找解决方案，而不是阻碍它们。我们有一个令人兴奋的机会，可以在分子水平上使用‘嘈杂物理学’的方法来探索进化本身的物理学，提出这个问题。“大自然是如何寻找并找到解决方案的？”完成这个项目的循环后，我们将构建粘性蛋白本身的进化理论。

How does order emerge from chaos? As if the 'miracle of life' in all its complexity were not enough to astonish us, the molecular story of how the information and energy flows occur within living cells and organisms tells an even stranger tale. For at the dimensions of life's molecular building blocks - the long protein molecules that fold up perfectly into functional forms, the even longer DNA that codes for the structure of its organisms, the cell membranes that marshal biochemical traffic between the cell and its surroundings - all these are subject to continual, rapid random fluctuation. The thermal jostling of every component seems, at first, to fight against the appearance of the order and structure that are the emergent signs of life. However, recent interdisciplinary collaborations between physicists and biologists have begun to discover just how deeply life has evolved to work with the noisy fluctuations rather than to fight them.This project will devote 5 years of focussed research to explore in detail three fundamental ways in which randomness and noise are recruited in biology, bringing the experience of the proposed Fellow, two post-doctoral research fellows and an extensive community of collaborators, to bear. The first example is right at the heart of information-processing in cells. 'Allostery' is the effect by which a protein molecule binds to another molecule (either a smaller species, or a giant molecule like DNA) if and only if a second 'signalling' molecule is also bound to it, at a different site. The presence of the signalling molecule is felt 'at a distance' at the other binding site. We will develop theoretical and computational tools to explore how the background of thermal fluctuations can be used to carry the signal, and learn from biology about the physics of fluctuating elastic matter.The second example continues the theme of protein-binding, but now to other proteins. The outstanding properties of spider and silkworm silk are even more outstanding when we discover how the fibres are made in nature. Somehow the molecular 'stickiness' of silk proteins is just enough to trigger their assembly into fibres when just the right flow conditions apply (at the spinneret). Working closely with experimental colleagues, we will develop theories of assembly in flow to help find out what makes silk, and its processing, so remarkable.A third stream of work takes the idea of random motion but now at the higher level of evolution itself. The search for the protein structures that deliver the binding properties of signalling and silk takes place in an unimaginably vast space of possibilities coded by the organism's genome. Random jumps in this space, like the random motions of the proteins themselves, somehow serve to find solutions, rather than frustrate them. We have an exciting opportunity to use the methods of 'noisy physics' at the molecular level to explore the physics of evolution itself, asking the question. 'How does nature search for, and find solutions?'. Completing the circle of the project, we will construct theories for the evolution of the sticky proteins themselves.