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Gating Mechanisms of Mechanosensitive Channels of Large Conductance, II: Systematic Study of Conformational Transitions

Yuye Tang ^*, Jejoong Yoo , Arun Yethiraj , Qiang Cui  and Xi Chen ^*

^* Nanomechanics Research Center, Department of Civil Engineering and Engineering Mechanics, Columbia University, New York, New York 10027; and Theoretical Chemistry Institute, Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706

Correspondence: Address reprint requests to Xi Chen, Tel.: 212-854-3787; Fax: 212-854-6267; E-mail: xichen{at}civil.columbia.edu.

Part II of this study is based on the continuum mechanics-based molecular dynamics-decorated finite element method (MDeFEM) framework established in Part I. In Part II, the gating pathways of Escherichia coli-MscL channels under various basic deformation modes are simulated. Upon equibiaxial 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, cooperativity, patch clamp, and indentation. Compared to atom-based molecular dynamics simulations and elastic network models, the MDeFEM framework is unusually well-suited for simulating complex deformations at large length scales. The versatile hierarchical framework can be further applied to simulate the gating transition of other mechanosensitive channels and other biological processes where mechanical perturbation is important.