Molecular Simulation of Ompf Channel in Salts of Divalent Cations: Molecular Insight on Charge Inversion

Abstract

Extensive recent experimental and theoretical work has shown that the interaction of biologically relevant divalent cations (such as Mg2+, Ca2+) has surprising properties. One of the most fascinating and unexpected effect is the so-called charge inversion or charge reversal phenomenon: cations accumulate at the interface in excess of its own bare charge, thus inverting the effective charge of the interface. Recently, charge inversion has been reported in the bacterial channel OmpF, in the presence of salts of divalent cations [Alcaraz et al. Biophys. J. 96 (2009) 56]. Aiming to get an insight on the atomistic mechanism of the cation interaction with the protein, we have performed extensive MD simulations of a realistic model of the OmpF WT protein in a POPC membrane in MgCl2 and explicit water. The simulations were computationally highly demanding, with half million atoms in a simulation box and production runs around 25 nsec.The simulations were performed employing the NAMD simulation package running in 128 processor at the CESGA Supercomputing Center. Our main result is that we have observed charge inversion of certain important acidic groups. The observed charge inversion is accompanied by a change in the transport mechanism of ions inside the channel and a reversal in the selectivity of the channel. Overall, our simulations give an accurate microscopic image of this unexpected effect with potentially important biological and nanotechnological implications.