This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Proposal Keywords alpha-Hemolysin ion permeation current flow ClC channel Potential of Mean Force Gramicidin molecular dynamics (MD) NAMD AMBER 7 Abstract: I. Non-Equilibrium Molecular Dynamics In Alpha-Hemolysin As a continuance to the work accomplished through our development grant (# mcb030021p) on the TCS cluster at PSC, we propose to perform further voltage-driven non-equilibrium Molecular Dynamics (NEMD) simulations of ion currents through alpha-hemolysin using NAMD. The initial calculations were carried out at high salt concentration (1M) and high voltage bias (1V), as well as at a lower voltage bias of 200mV, producing results that are qualitatively accurate with regards to selectivity and rectification as well as comparable to those produced via Poisson Nernst-Planck (PNP) simulation. The structure of alpha-hemolysin was fixed throughout these simulations in order to reduce computational requirements. Further calculations will be performed at experimental conditions of 1M salt concentration and -500mV to 500mV applied voltage bias, with the residues at the protein-solvent interface free to move as to further resemble realistic model perturbations. This method will require a long time scale (> 100 ns total simulation time) and so will be very inefficient to perform on our serial machines (a 12-node cluster). Running this computation on parallel machines on the Lemieux cluster will greatly reduce real-time requirements. The system to be simulated will consist of alpha-Hemolysin embedded in a layer of neutral dummy atoms and solvated by NaCl solution. Ion current will be generated by application of an electric field as per an embedded function in NAMD. Current-Voltage characteristics will be compared with the results obtained via another computational method, Poisson-Nernst-Planck continuum approach.
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