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Computational Design of Membrane Proteins pp 141–159Cite as

Molecular Dynamics Simulation of Lipid-Modified Signaling Proteins

Part of the Methods in Molecular Biology book series (MIMB,volume 2315)

Abstract

In this chapter, we provide a practical guide on how to plan, execute, and interpret atomistic and coarse-grained molecular dynamics (MD) simulations of lipid-modified proteins in model membranes. After outlining some key practical considerations when planning such simulations, we survey resources and techniques to obtain force field parameters for nonconventional amino acids, such as posttranslationally lipid-modified amino acids that are unique to this class of proteins. We then describe the protocols to build, setup, and run the simulations, followed by a brief comment on the analysis and interpretation of the simulations. Finally, examples of insights that could be gained from atomistic and coarse-grained MD simulations of lipidated proteins will be provided, using RAS proteins as illustrative examples. Throughout the chapter, we highlight the main advantages and limitations of simulating RAS and related lipid-modified G-proteins in biomimetic membranes.

Key words

  • Lipidated proteins
  • Membrane
  • Lipid bilayer
  • Molecular dynamics simulation
  • G-proteins

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Acknowledgments

This work was supported in part by the National Institutes of Health grant R01GM124233 and the Cancer Prevention and Research Institute of Texas (CPRIT) grant RP190366. V.N. is supported by UTHealth Innovation for Cancer Prevention Research Training Program Pre-Doctoral Fellowship (Cancer Prevention and Research Institute of Texas grant RP160015).

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Authors and Affiliations

  1. Department of Integrative Biology & Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA

    Vinay V. Nair & Alemayehu A. Gorfe

  2. MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, TX, USA

    Vinay V. Nair & Alemayehu A. Gorfe

Authors
  1. Vinay V. Nair
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  2. Alemayehu A. Gorfe
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Correspondence to Alemayehu A. Gorfe .

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Editors and Affiliations

  1. Department of Life Sciences, University of Coimbra, Coimbra, Portugal

    Dr. Irina S. Moreira

  2. BioISI, University of Lisboa, Lisboa, Portugal

    Miguel Machuqueiro

  3. Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Joana Mourão

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Nair, V.V., Gorfe, A.A. (2021). Molecular Dynamics Simulation of Lipid-Modified Signaling Proteins. In: Moreira, I.S., Machuqueiro, M., Mourão, J. (eds) Computational Design of Membrane Proteins. Methods in Molecular Biology, vol 2315. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1468-6_9

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  • DOI: https://doi.org/10.1007/978-1-0716-1468-6_9

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