I am interested in using MD simulations towards physiologically relevant systems.  Towards this end, I have been examining proton transfer in a recently discovered voltage gated proton-selective channel, Hv1, that functions in human granulocytic phagocytes to neutralize the cell during the oxidative burst used to clear bacterial pathogens.  Hv1 is a unique system because while many ion channels contain a voltage sensing domain and a pore domain, this proton channel lacks a pore. We are using a homology model of Hv1 based upon the known structure of the voltage sensing domain of potassium channel Kv1.2 to probe the proton transport mechanism. My current project is interested in using free energy calculations aimed at understanding the structure and function of Hv1. Specifically, I am using QM/MM to do umbrella sampling with the weighted histogram analysis method (WHAM) to calculate a potential of mean force for a proton moving across a proposed water wire through the center of the channel.