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Molecular Dynamics–Based Thermodynamic and Kinetic Characterization of Membrane Protein Conformational Transitions

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Structure and Function of Membrane Proteins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2302))

Abstract

Molecular dynamics (MD) simulations are routinely used to study structural dynamics of membrane proteins. However, conventional MD is often unable to sample functionally important conformational transitions of membrane proteins such as those involved in active membrane transport or channel activation process. Here we describe a combination of multiple MD based techniques that allows for a rigorous characterization of energetics and kinetics of large-scale conformational changes in membrane proteins. The methodology is based on biased, nonequilibrium, collective-variable based simulations including nonequilibrium pulling, string method with swarms of trajectories, bias-exchange umbrella sampling, and rate estimation techniques.

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Acknowledgments

This material is based upon work supported by the National Science Foundation under grant numbers 1940188 and 1945465. This research is also supported by the Arkansas Biosciences Institute. This work used the Extreme Science and Engineering Discovery Environment (allocation MCB150129), which is supported by National Science Foundation grant number ACI-1548562. This research is also supported by the Arkansas High Performance Computing Center which is funded through multiple National Science Foundation grants and the Arkansas Economic Development Commission.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR, USA

    Dylan Ogden & Mahmoud Moradi

Authors
  1. Dylan Ogden
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  2. Mahmoud Moradi
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Correspondence to Mahmoud Moradi .

Editor information

Editors and Affiliations

  1. School of Biological Sciences and School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA

    Ingeborg Schmidt-Krey

  2. School of Physics, Georgia Institute of Technology, Atlanta, GA, USA

    James C. Gumbart

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Ogden, D., Moradi, M. (2021). Molecular Dynamics–Based Thermodynamic and Kinetic Characterization of Membrane Protein Conformational Transitions. In: Schmidt-Krey, I., Gumbart, J.C. (eds) Structure and Function of Membrane Proteins. Methods in Molecular Biology, vol 2302. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1394-8_16

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  • DOI: https://doi.org/10.1007/978-1-0716-1394-8_16

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1393-1

  • Online ISBN: 978-1-0716-1394-8

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