Towards understanding the mechanism of fast proton transport in biological systems

氢键给体和受体原子之间的快速质子输运（PT）在化学和生物学的许多方面都是至关重要的。从基本的角度来看，它是电池实现pH稳定性并将能量从一种形式转化为另一种形式的机制;从材料的角度来看，它支撑了许多技术发展，如氢燃料电池。通过实验研究PT反应是非常复杂的，因为该过程发生在极短的时间尺度上（约200年）。10飞秒）。工作仅限于小分子系统的研究，需要非常专业的仪器，结果是很难在文献中获得直接的实验证据。我们的目的是了解PT在生物应用中的机制，使用模拟。然而，这并非没有其自身的一系列挑战，这些挑战是三方面的。首先，键的形成和断裂事件排除了使用传统的（和计算便宜）分子力学力场。其次，由于氢原子的质量很小，量子效应，如隧道效应和零点能量贡献，可以从根本上改变反应的景观。第三，PT是一种边缘罕见事件，这意味着在大多数时间系统处于静止状态，对分子动力学轨迹的统计采样有明显的影响。本申请旨在了解PT通过膜结合蛋白发生的机制。我们已经建立了一个适应性强的模型系统，它足够复杂，可以封装基本的分子框架，但又足够小，可以进行从头算和路径积分分子动力学计算，以解决上述挑战。我们已经进行了测试计算野兔（EaSTCHEM研究计算设施）和蓝色基因（爱丁堡并行计算中心），并验证了我们的程序，但我们受到内存限制和处理器的数量提供给我们。出于这些原因，我们现在寻求访问HPCx。

Fast proton transport (PT) between hydrogen-bond donor and acceptor atoms is of paramount importance in many aspects of chemistry and biology. From a fundamental perspective it is the mechanism by which cells achieve pH stability and can convert energy from one form into another; from a materials perspective it underpins many technological developments such as hydrogen fuel cells. To study PT reactions experimentally is very complex, as the process occurs over extremely short timescales (ca. 10 femtoseconds). Work is confined to the study of small molecule systems and very specialised apparatus is required, with the consequence that direct experimental evidence in the literature is hard to come by. Our aim is to understand the mechanism of PT in biological applications using simulation. This is not without its own set of challenges, however, which are three-fold. First, bond formation and breaking events rule out the use of conventional (and computationally inexpensive) molecular mechanics force fields. Second, owing to the small mass of the hydrogen atom, quantum effects such as tunnelling and zero-point energy contributions can radically alter the reaction landscape. Third, PT is a borderline rare event, meaning that for the majority of the time the system is at rest, with obvious consequences for statistical sampling from molecular dynamics trajectories. This application is directed towards understanding the mechanism by which PT takes place through membrane-bound proteins. We have built an adaptable model system that is complex enough to encapsulate the essential molecular framework, and yet small enough to be accessible to ab initio and path integral molecular dynamics calculations that would address the challenges highlighted above. We have performed test calculations on Hare (EaSTCHEM Research Computing Facility) and Blue Gene (Edinburgh Parallel Computing Centre) and have validated our procedures, but we are constrained by memory limitations and the number of processors available to us. For these reasons we now seek access to HPCx.