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

秩序是如何从混乱中产生的？仿佛“生命的奇迹”在其所有的复杂性都不足以让我们着迷，关于活细胞和生物体内信息和能量流动如何发生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，编码其有机体结构的更长的DNA，在细胞与其周围环境之间指挥生化运输的细胞膜--所有这些都受到持续的、快速的随机波动的影响。起初，每一个组成部分的热碰撞似乎都在与生命的秩序和结构的出现作斗争，而秩序和结构是生命的涌现迹象。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声波动一起工作而不是与它们斗争的程度有多深。这个项目将花费5年的时间进行重点研究，详细探索生物学中随机性和噪声招募的三种基本方式，带来拟议研究员的经验，两名博士后研究员和一个广泛的合作者社区，承担。第一个例子是细胞信息处理的核心。“Allostery”是当且仅当第二个“信号”分子也在不同的位点与蛋白质分子结合时，蛋白质分子与另一个分子（较小的物种或像DNA这样的巨大分子）结合的效果。信号分子的存在在另一个结合位点处被"远距离"感觉到。我们将开发理论和计算工具来探索如何利用热涨落的背景来携带信号，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，但现在是其他蛋白质。蜘蛛丝和蚕丝的卓越性能在我们发现纤维是如何在自然界中形成的时更加突出。不知何故，丝蛋白的分子“粘性”刚好足以触发它们在合适的流动条件下组装成纤维。与实验同事密切合作，我们将发展流动中的组装理论，以帮助找出是什么使丝及其加工如此可行。第三个工作流采用随机运动的想法，但现在是在进化本身的更高水平上。对传递信号和丝的结合特性的蛋白质结构的搜索发生在由生物体基因组编码的无限广阔的可能性空间中。这个空间中的随机跳跃，就像蛋白质本身的随机运动一样，在某种程度上有助于找到解决方案，而不是挫败它们。我们有一个令人兴奋的机会在分子水平上使用“噪声物理学”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，我们将构建粘性蛋白质本身进化的理论。

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.