BIOPHYSICAL THEORY AND MODELING |
Mechanosensitive membrane channels in action
Serge Yefimov 1, Erik van der Giessen 1*, Patrick Onck 1 and Siewert J Marrink 1
1 University of Groningen
* To whom correspondence should be addressed. E-mail: e.van.der.giessen{at}rug.nl.
Submitted on August 16, 2007
Revised on October 5, 2007
Accepted on 22 October 2007
 |
Abstract |
|---|
The tension-driven gating process of MscL from Mycobacterium tuberculosis, Tb-MscL, has been addressed at near-atomic detail using coarse grained (CG) molecular dynamics simulations. To perform the simulations a novel CG 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 (GOF) 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 iris-like expansion mechanism, reaching a conducting state on a microsecond time scale. The most pronounced expansion of the pore has been observed for the V21D mutant,which is consistent with the experimentally shown GOF phenotype of the V21D mutant.
Key Words:
MscL, coarse grained, computational model, gating, molecular dynamics, osmotic shock
