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Combining NMR and Molecular Dynamics Studies for Insights into the Allostery of Small GTPase–Protein Interactions

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Allostery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 796))

Abstract

Combinations of experimentally derived data from nuclear magnetic resonance spectroscopy and analyses of molecular dynamics trajectories increasingly allow us to obtain a detailed description of the molecular mechanisms by which proteins function in signal transduction. This chapter provides an introduction into these two methodologies, illustrated by example of a small GTPase–effector interaction. It is increasingly becoming clear that new insights are provided by the combination of experimental and computational methods. Understanding the structural and protein dynamical contributions to allostery will be useful for the engineering of new binding interfaces and protein functions, as well as for the design/in silico screening of chemical agents that can manipulate the function of small GTPase–protein interactions in diseases such as cancer.

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Acknowledgments

We thank Shufen Cao, Dr. Prasanta K. Hota, and other members of the Buck laboratory for insightful discussion, as well as Dr. Aron Fenton for editorial help. Some of the molecular dynamics calculations were carried out by Dr. Mehdi Bagheri Hamaneh at the Case Western Reserve High Performance Cluster and at Lonestar (Austin, TX, USA) via a TeraGrid award (to M. B.). The work of M. B. is supported by the NIH grants 1R01GM092851, 1K02HL084384, and 1R01GM73071, which included an ARRA supplement.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Liqun Zhang

  2. Methodologie RMN (CRM2; UMR 7036, UHP-CNRS), Faculté des Sciences et Techniques, Nancy-Université, Vandoeuvre-les-Nancy, France

    Sabine Bouguet-Bonnet

  3. Department of Physiology and Biophysics, Case Comprehensive Cancer Center, Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Matthias Buck

  4. Department of Neurosciences, Case Comprehensive Cancer Center, Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Matthias Buck

  5. Department of Pharmacology, Case Comprehensive Cancer Center, Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Matthias Buck

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  1. Liqun Zhang
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  2. Sabine Bouguet-Bonnet
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  3. Matthias Buck
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Correspondence to Matthias Buck .

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Editors and Affiliations

  1. , Dept. Biochemistry & Molecular Biology, University of Kansas Medical Center, Rainbow Blvd. 3901, Kansas City, 66160, Kansas, USA

    Aron W. Fenton

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Zhang, L., Bouguet-Bonnet, S., Buck, M. (2012). Combining NMR and Molecular Dynamics Studies for Insights into the Allostery of Small GTPase–Protein Interactions. In: Fenton, A. (eds) Allostery. Methods in Molecular Biology, vol 796. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-334-9_13

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  • DOI: https://doi.org/10.1007/978-1-61779-334-9_13

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