BIOPHYSICAL THEORY AND MODELING |
Gating Mechanisms of Mechanosensitive Channels of Large Conductance Part II: Systematic Study of Conformational Transitions
Yuye Tang 1, Jejoong Yoo 2, Arun Yethiraj 3, Qiang Cui 4 and Xi Chen 1*
1 Columbia University
2 University of Wisconsin-Madison
3 University of Wisconsin
4 University of Wisconsin, Madison
* To whom correspondence should be addressed. E-mail: xichen{at}civil.columbia.edu.
Submitted on December 27, 2007
Revised on January 26, 2008
Accepted on 18 March 2008
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Abstract |
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Based on the continuum mechanics-based molecular dynamics-decorated finite element method (MDeFEM) framework established in Part I of this paper, in Part II, the gating pathways of E.coli-MscL channels under various basic deformation modes are simulated. Upon equi-biaxial tension (which is verified to be the most effective mode for gating), the MDeFEM results agree well with both experiments and all-atom simulations in literature, as well as the analytical continuum models and elastic network models developed in Part I. Different levels of model sophistication and effects of structural motifs are explored in detail, where the importance of mechanical roles of transmembrane helices, cytoplasmic helices and loops are discussed. The conformation transitions under complex membrane deformations are predicted, including bending, torsion, co-operativity, patch clamp and indentation. Compared to atom-based molecular dynamics simulations and elastic network models, the MDeFEM framework is uniquely suited for simulating complex deformations at large length scales. The versatile hierarchical framework can be further applied to simulate the gating transition of other MS channels and other biological processes where mechanical perturbation is important.
Key Words:
elastic network model, finite element analysis, gating, mechanosensitive channel
