UC Irvine

Molecular Dynamics simulations were used to study a variety of biophysical systems. The first of these used multi-microsecond simulations to model the activation of the Hv1 voltage-gated proton channel under a depolarizing membrane potential. The generated model reproduced several important experimental measurements and provided insight into the conformational change of the protein in response to the membrane potential. The second project involved modeling several different voltage-gated K+ channels in open and closed states to compare with neutron and x-ray scattering experiments. Voltage-dependent changes in the membrane profile structure and comparison with atomistic models demonstrated a large inward translation of the voltage-sensing domain S4 helix and a de-wetting of the cytoplasmic half of the pore. The third project utilized multi-microsecond simulations of two peripheral membrane proteins, the C2 domain and PH domain, to study their diffusion on the membrane surface. Both proteins were found to exhibit anomalous diffusion for timescales on the order of 10 ns. Lastly, various statistical analyses were performed on trajectories of the mechanosensitive Piezo1 ion channel obtained using single-particle tracking experiments to elucidate the behavior of the diffusion. The Piezo1 motion was found to be subdiffusive, relying on a mixed model to describe the behavior.