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Continuous Constant pH Molecular Dynamics Simulations of Transmembrane Proteins

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Structure and Function of Membrane Proteins

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

Abstract

Many membrane channels, transporters, and receptors utilize a pH gradient or proton coupling to drive functionally relevant conformational transitions. Conventional molecular dynamics simulations employ fixed protonation states, thus neglecting the coupling between protonation and conformational equilibria. Here we describe the membrane-enabled hybrid-solvent continuous constant pH molecular dynamics method for capturing atomic details of proton-coupled conformational dynamics of transmembrane proteins. Example protocols from our recent application studies of proton channels and ion/substrate transporters are discussed.

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Acknowledgments

The authors acknowledge the National Institutes of Health (R01GM098818 and R01GM118772) for funding. Yandong Huang and Jack A. Henderson contributed equally to this work.

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Author notes

  1. Yandong Huang and Jack A. Henderson contributed equally with all other contributors.

Authors and Affiliations

  1. College of Computer Engineering, Jimei University, Xiamen, Fujian, China

    Yandong Huang

  2. University of Maryland School of Pharmacy, Baltimore, MD, USA

    Jack A. Henderson & Jana Shen

Authors
  1. Yandong Huang
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  2. Jack A. Henderson
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  3. Jana Shen
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Corresponding author

Correspondence to Jana Shen .

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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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Huang, Y., Henderson, J.A., Shen, J. (2021). Continuous Constant pH Molecular Dynamics Simulations of Transmembrane Proteins. 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_15

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  • DOI: https://doi.org/10.1007/978-1-0716-1394-8_15

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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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