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Mechanosensitive Membrane Channels in Action

Serge Yefimov ^*, Erik van der Giessen ^*, Patrick R. Onck ^* and Siewert J. Marrink 

^* Zernike Institute for Advanced Materials, Department of Applied Physics, and Groningen Biomolecular Sciences and Biotechnology Institute, Department of Biophysical Chemistry, University of Groningen, Nijenborgh, Groningen, The Netherlands

Correspondence: Address reprint requests to Erik van der Giessen, E-mail: e.van.der.giessen{at}rug.nl.

The tension-driven gating process of MscL from Mycobacterium tuberculosis, Tb-MscL, has been addressed at near-atomic detail using coarse-grained molecular dynamics simulations. To perform the simulations, a novel coarse-grained peptide model based on a thermodynamic parameterization of the amino-acid side chains has been applied. Both the wild-type Tb-MscL and its gain-of-function mutant V21D embedded in a solvated lipid bilayer have been studied. To mimic hypoosmotic shock conditions, simulations were performed at increasing levels of membrane tension approaching the rupture threshold of the lipid bilayer. Both the wild-type and the mutant channel are found to undergo significant conformational changes in accordance with an irislike expansion mechanism, reaching a conducting state on a microsecond timescale. The most pronounced expansion of the pore has been observed for the V21D mutant, which is consistent with the experimentally shown gain-of-function phenotype of the V21D mutant.