Towards understanding the mechanism of fast proton transport in biological systems

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.