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Molecular Dynamics Simulations of Wild-Type and Mutant Forms of the Mycobacterium tuberculosis MscL Channel

Elmore, Donald E. and Dougherty, Dennis A. (2001) Molecular Dynamics Simulations of Wild-Type and Mutant Forms of the Mycobacterium tuberculosis MscL Channel. Biophysical Journal, 81 (3). pp. 1345-1359. ISSN 0006-3495. PMCID PMC1301615. doi:10.1016/s0006-3495(01)75791-8.

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The crystal structure of the Mycobacterium tuberculosis homolog of the bacterial mechanosensitive channel of large conductance (Tb-MscL) provides a unique opportunity to consider mechanosensitive signal transduction at the atomic level. Molecular dynamics simulations of the Tb-MscL channel embedded in an explicit lipid bilayer and of its C-terminal helical bundle alone in aqueous solvent were performed. C-terminal calculations imply that although the helix bundle structure is relatively unstable at physiological pH, it may have been stabilized under low pH conditions such as those used in the crystallization of the channel. Specific mutations to the C-terminal region, which cause a similar conservation of the crystal structure conformation, have also been identified. Full channel simulations were performed for the wild-type channel and two experimentally characterized gain-of-function mutants, V21A and Q51E. The wild-type Tb-MscL trajectory gives insight into regions of relative structural stability and instability in the channel structure. Channel mutations led to observable changes in the trajectories, such as an alteration of intersubunit interactions in the Q51E mutant. In addition, interesting patterns of protein-lipid interactions, such as hydrogen bonding, arose in the simulations. These and other observations from the simulations are relevant to previous and ongoing experimental studies focusing on characterization of the channel.

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Dougherty, Dennis A.0000-0003-1464-2461
Additional Information:© 2001 The Biophysical Society. Published by Elsevier Inc. All rights reserved. Received 29 January 2001, Accepted 2 May 2001. We are grateful to Prof. Kenneth Philipson and Joshua Maurer for their insightful suggestions throughout the project and to Prof. Douglas Rees, Prof. Henry Lester, and Steve Spronk for additional helpful discussions. The pre-equilibrated POPE membrane structure was generously provided by Prof. D. P. Tieleman.
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Issue or Number:3
PubMed Central ID:PMC1301615
Record Number:CaltechAUTHORS:20200504-153931338
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Official Citation:Donald E. Elmore, Dennis A. Dougherty, Molecular Dynamics Simulations of Wild-Type and Mutant Forms of the Mycobacterium tuberculosis MscL Channel, Biophysical Journal, Volume 81, Issue 3, 2001, Pages 1345-1359, ISSN 0006-3495,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102986
Deposited By: Ian Roberts
Deposited On:04 May 2020 23:34
Last Modified:16 Nov 2021 18:17

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