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Network Re-Wiring During Allostery and Protein-Protein Interactions: A Graph Spectral Approach

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Allostery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2253))

Abstract

The process of allostery is often guided by subtle changes in the non-covalent interactions between residues of a protein. These changes may be brought about by minor perturbations by natural processes like binding of a ligand or protein-protein interaction. The challenge lies in capturing minute changes at the residue interaction level and following their propagation at local as well as global distances. While macromolecular effects of the phenomenon of allostery are inferred from experiments, a computational microscope can elucidate atomistic-level details leading to such macromolecular effects. Network formalism has served as an attractive means to follow this path and has been pursued further for the past couple of decades. In this chapter some concepts and methods are summarized, and recent advances are discussed. Specifically, the changes in strength of interactions (edge weight) and their repercussion on the overall protein organization (residue clustering) are highlighted. In this review, we adopt a graph spectral method to probe these subtle changes in a quantitative manner. Further, the power of this method is demonstrated for capturing re-ordering of side-chain interactions in response to ligand binding, which culminates into formation of a protein-protein complex in β2-adrenergic receptors.

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Acknowledgments

S.V. thanks National Academy of Sciences (NASI), Allahabad, India, for Senior Scientist Fellowship. V.G. thanks IISc for incentive research support grant and CSIR for Research Associate fellowship. We thank SERC and MBU of the Indian Institute of Science for computational facilities.

Author information

Author notes

  1. Vasundhara Gadiyaram

    Present address: Department of Biochemistry, Biophysics and Bioinformatics, National Center for Biological Sciences, Bangalore, India

  2. Anasuya Dighe

    Present address: Systems Biology Institute, Yale University West Campus, West Haven, CT, USA

  3. Sambit Ghosh

    Present address: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA

  4. Vasundhara Gadiyaram and Anasuya Dighe contributed equally to the work.

Authors and Affiliations

  1. IISc Mathematics Initiative (IMI), Indian Institute of Science, Bangalore, India

    Vasundhara Gadiyaram & Anasuya Dighe

  2. Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India

    Sambit Ghosh & Saraswathi Vishveshwara

Authors
  1. Vasundhara Gadiyaram
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  2. Anasuya Dighe
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  3. Sambit Ghosh
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  4. Saraswathi Vishveshwara
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Corresponding author

Correspondence to Saraswathi Vishveshwara .

Editor information

Editors and Affiliations

  1. Unit of Chemical-Physics Fundamentals in Chemical Engineering Department of Engineering, Universitá Campus Bio-Medico di Rome, Rome, Italy

    Luisa Di Paola

  2. Environment and Health Department, Instituto Superiore di Sanità, Rome, Italy

    Alessandro Giuliani

1 Electronic Supplementary Material

Data 1

Residue clustering in β2AR-Gs (XLSX 33 kb)

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Gadiyaram, V., Dighe, A., Ghosh, S., Vishveshwara, S. (2021). Network Re-Wiring During Allostery and Protein-Protein Interactions: A Graph Spectral Approach. In: Di Paola, L., Giuliani, A. (eds) Allostery. Methods in Molecular Biology, vol 2253. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1154-8_7

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  • DOI: https://doi.org/10.1007/978-1-0716-1154-8_7

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1153-1

  • Online ISBN: 978-1-0716-1154-8

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