Web Interface for Brownian Dynamics Simulation of Ion Transport and Its Application to Beta-Barrel Pores

This is the peer reviewed version of the following article: Lee, K. I., Jo, S., Rui, H., Egwolf, B., Roux, B., Pastor, R. W., & Im, W. (2012). Web Interface for Brownian Dynamics Simulation of Ion Transport and Its Applications to Beta-Barrel Pores. Journal of Computational Chemistry, 33(3), 331–339. http://doi.org/10.1002/jcc.21952, which has been published in final form at http://doi.org/10.1002/jcc.21952. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Brownian dynamics (BD) in a suitably constructed potential of mean force is an efficient and accurate method for simulating ion transport through wide ion channels. Here, a web-based graphical user interface (GUI) is presented for grand canonical Monte Carlo (GCMC) BD simulations of channel proteins: http://www.charmm-gui.org/input/gcmcbd. The webserver is designed to help users avoid most of the technical difficulties and issues encountered in setting up and simulating complex pore systems. GCMC/BD simulation results for three proteins, the voltage dependent anion channel (VDAC), α-Hemolysin, and the protective antigen pore of the anthrax toxin (PA), are presented to illustrate system setup, input preparation, and typical output (conductance, ion density profile, ion selectivity, and ion asymmetry). Two models for the input diffusion constants for potassium and chloride ions in the pore are compared: scaling of the bulk diffusion constants by 0.5, as deduced from previous all-atom molecular dynamics simulations of VDAC; and a hydrodynamics based model (HD) of diffusion through a tube. The HD model yields excellent agreement with experimental conductances for VDAC and α-Hemolysin, while scaling bulk diffusion constants by 0.5 leads to underestimates of 10–20%. For PA, simulated ion conduction values overestimate experimental values by a factor of 1.5 to 7 (depending on His protonation state and the transmembrane potential), implying that the currently available computational model of this protein requires further structural refinement