Simulations for Synthetic Biology: Mapping Biological Switches

我们的身体是由许多称为细胞的小积木组成的。每个细胞都在不断吸收营养，接收来自身体其他部位的信号，并输出废物和产品。这些重要功能是由每个细胞内产生的大分子（称为蛋白质）执行的。细胞通过打开和关闭蛋白质来控制这些功能。我们不太清楚蛋白质是如何在这些状态之间转换的。合成生物学和生物纳米技术领域的研究人员受到了这种复杂性的启发，并试图设计和构建自己的分子来做某些事情。他们还希望他们的合成分子能够在不同的状态之间切换。在这项研究中，我们计划研究蛋白质的一部分，称为α-螺旋，如何能够通过中间的扭结采用不同的结构。这已经被其他研究人员研究过了，然而，我们计划计算地图，显示每个切换状态的位置以及α螺旋在两个状态之间移动的容易程度。这直到现在还不可能，因为需要非常大量的快速计算机来运行所有必要的模拟。我们计划使用英国国家超级计算机之一HPCx来运行这些模拟。我们还将研究改变每个α螺旋周围的环境如何影响其转换能力。因此，我们的研究不仅将揭示蛋白质如何能够在状态之间切换，还将帮助其他研究人员设计和构建合成分子。

Our bodies are made up of many small building blocks called cells. Each cell is constantly drawing in nutrients, receive signals from elsewhere in the body and export waste and products. These vital functions are performed by large molecules, called proteins, that are made within each cell. The cell controls these functions by switching the proteins on and off. We do not understand very well how proteins are able to switch between these states. Researchers in the synthetic biology and bionanotechnology fields have been inspired by this complexity and are trying to design and build their own molecules that do certain things. They also want their synthetic molecules to be able to switch between different states. In this study we plan to investigate how parts of proteins, called alpha-helices, are able to adopt different structures by kinking in the middle. This has been looked at by other researchers, however, we plan to compute maps showing where each of the switched states is and how easily the alpha-helix can move between the two states. This has not been possible until now because a very large number of fast computers are required to run all the necessary simulations. We plan to use HPCx, one of the UK's national supercomputers, to run these simulations. We shall also study how changing the environment around each alpha-helix affects its ability to switch. Our study will therefore not only shed light on how proteins are able to switch between states but will also help other researchers design and build synthetic molecules.