Towards understanding the mechanism of fast proton transport in biological systems

理解生物系统中快速质子传输的机制

• 批准号: EP/G040656/1
• 负责人: Carole Morrison
• 金额: $ 1.35万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG040656%2F1
• 关键词: Towards; understanding; mechanism; fast; proton

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.

氢键供体和受体原子之间的快速质子传递（PT）在化学和生物学的许多方面具有至关重要的意义。从基本的角度来看，它是细胞实现pH稳定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，它是氢燃料电池等许多技术发展的基础。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（约10飞秒）。工作局限于小分子系统的研究，需要非常专业的仪器，结果是文献中的直接实验证据很难得到。我们的目的是通过模拟来了解PT在生物应用中的机制。然而，这并非没有自己的一系列挑战，这些挑战有三个方面。首先，键的形成和断裂事件排除了传统的（计算成本不高的）分子力学力场的使用。其次，由于氢原子的质量很小，隧道效应和零点能量贡献等量子效应可以从根本上改变反应的格局。第三，PT是一种边缘性罕见事件，这意味着在大多数时间里系统处于静止状态，这对分子动力学轨迹的统计采样有明显的影响。该应用旨在理解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，以解决上面强调的挑战。我们已经在Hare （EaSTCHEM研究计算设施）和Blue Gene（爱丁堡并行计算中心）上进行了测试计算，并验证了我们的程序，但我们受到内存限制和可用处理器数量的限制。由于这些原因，我们现在寻求访问HPCx。