title: Nanomechanical properties of MscL α helices: A steered molecular dynamics study.
abstract: Gating of mechanosensitive (MS) channels is driven by a hierarchical cascade of movements and deformations of transmembrane helices in response to bilayer tension. Determining the intrinsic mechanical properties of the individual transmembrane helices is therefore central to understanding the intricacies of the gating mechanism of MS channels. We used a constant-force steered molecular dynamics (SMD) approach to perform unidirectional pulling tests on all the helices of MscL in M. tuberculosis and E. coli homologs. Using this method, we could overcome the issues encountered with the commonly used constant-velocity SMD simulations, such as low mechanical stability of the helix during stretching and high dependency of the elastic properties on the pulling rate. We estimated Young's moduli of the α-helices of MscL to vary between 0.2 and 12.5 GPa with TM2 helix being the stiffest. We also studied the effect of water on the properties of the pore-lining TM1 helix. In the absence of water, this helix exhibited a much stiffer response. By monitoring the number of hydrogen bonds, it appears that water acts like a 'lubricant' (softener) during TM1 helix elongation. These data shed light on another physical aspect underlying hydrophobic gating of MS channels, in particular MscL.
authors.affiliation: a Division of Molecular Cardiology and Biophysics , Victor Chang Cardiac Research Institute , Darlinghurst , NSW , Australia.|b St Vincent's Clinical School, Faculty of Medicine , University of New South Wales , Darlinghurst , NSW , Australia.
authors.forename: N
authors.initials: N
authors.lastname: Bavi
authors.affiliation: c Institute for Nanoscience and Nanotechnology, Sharif University of Technology , Tehran , Iran.
authors.forename: O
authors.initials: O
authors.lastname: Bavi
authors.affiliation: c Institute for Nanoscience and Nanotechnology, Sharif University of Technology , Tehran , Iran.|d Biochemical & Bioenvironmental Research Center (BBRC) , Tehran , Iran.
authors.forename: M
authors.initials: M
authors.lastname: Vossoughi
authors.affiliation: c Institute for Nanoscience and Nanotechnology, Sharif University of Technology , Tehran , Iran.|e Department of Mechanical Engineering , Sharif University of Technology , Tehran , Iran.
authors.forename: R
authors.initials: R
authors.lastname: Naghdabadi
authors.affiliation: a Division of Molecular Cardiology and Biophysics , Victor Chang Cardiac Research Institute , Darlinghurst , NSW , Australia.
authors.forename: A P
authors.initials: AP
authors.lastname: Hill
authors.affiliation: a Division of Molecular Cardiology and Biophysics , Victor Chang Cardiac Research Institute , Darlinghurst , NSW , Australia.|b St Vincent's Clinical School, Faculty of Medicine , University of New South Wales , Darlinghurst , NSW , Australia.
authors.forename: B
authors.initials: B
authors.lastname: Martinac
authors.affiliation: f Department of Mathematics , Tarbiat Modares University , Tehran , Iran.|g Computational Physical Sciences Research Laboratory , School of Nanoscience, Institute for Research in Fundamental Sciences (IPM) , Tehran , Iran.
authors.forename: Y
authors.initials: Y
authors.lastname: Jamali
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001696:Biomechanical Phenomena; D004548:Elasticity; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D055595:Mechanical Phenomena; D056004:Molecular Dynamics Simulation; D036103:Nanotechnology; D016062:Porosity; D000072756:Protein Conformation, alpha-Helical
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007473:Ion Channels; C086596:MscL protein, E coli; C116377:Tb-MscL protein, Mycobacterium tuberculosis
keywords: Escherichia coli; Young's modulus; all-atom simulation; constant velocity; mechanosensitive channel; mycobacterium tuberculosis; nanovalve