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Voltage-Dependent Hydration and Conduction Properties of the Hydrophobic Pore of the Mechanosensitive Channel of Small Conductance

Steven A. Spronk ^*, Donald E. Elmore  and Dennis A. Dougherty ^*

^* Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California; and Chemistry Department, Wellesley College, Wellesley, Massachusetts

Correspondence: Address reprint requests to Dennis A. Dougherty, E-mail: dad{at}igor.caltech.edu

A detailed picture of water and ion properties in small pores is important for understanding the behavior of biological ion channels. Several recent modeling studies have shown that small, hydrophobic pores exclude water and ions even if they are physically large enough to accommodate them, a mechanism called hydrophobic gating. This mechanism has been implicated in the gating of several channels, including the mechanosensitive channel of small conductance (MscS). Although the pore in the crystal structure of MscS is wide and was initially hypothesized to be open, it is lined by hydrophobic residues and may represent a nonconducting state. Molecular dynamics simulations were performed on MscS to determine whether or not the structure can conduct ions. Unlike previous simulations of hydrophobic nanopores, electric fields were applied to this system to model the transmembrane potential, which proved to be important. Although simulations without a potential resulted in a dehydrated, occluded pore, the application of a potential increased the hydration of the pore and resulted in current flow through the channel. The calculated channel conductance was in good agreement with experiment. Therefore, it is likely that the MscS crystal structure is closer to a conducting than a nonconducting state.

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