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Prediction of Protein–Protein Binding Affinities from Unbound Protein Structures

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Computational Methods for Estimating the Kinetic Parameters of Biological Systems

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2385))

Abstract

Proteins are the workhorses of cells to carry out sophisticated and complex cellular processes. Such processes require a coordinated and regulated interactions between proteins that are both time and location specific. The strength, or binding affinity, of protein–protein interactions ranges between the micro- and the nanomolar association constant, often dictating the molecular mechanisms underlying the interaction and the longevity of the complex, i.e., transient or permanent. In consequence, there is a need to quantify the strength of protein–protein interactions for biological, biomedical, and biotechnological applications. While experimental methods are labor intensive and costly, computational ones are useful tools to predict the affinity of protein–protein interactions. In this chapter, we review the methods developed by us to address this question. We briefly present two methods to comprehend the structure of the protein complex derived by either comparative modeling or docking. Then we introduce BADOCK, a method to predict the binding energy without requiring the structure of the protein complex, thus overcoming one of the major limitations of structure-based methods for the prediction of binding affinity. BADOCK utilizes the structure of unbound proteins and the protein docking sampling space to predict protein–protein binding affinities. We present step-by-step protocols to utilize these methods, describing the inputs and potential pitfalls as well as their respective strengths and limitations.

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Authors and Affiliations

  1. Structural Bioinformatics Lab (GRIB-IMIM), Department of Experimental and Health Science, University Pompeu Fabra, Barcelona, Catalonia, Spain

    Alberto Meseguer, Patricia Bota & Baldo Oliva

  2. Department of Biosciences, U Science Tech, Universitat de Vic-Universitat Central de Catalunya, Catalonia, Spain

    Patricia Bota & Narcis Fernández-Fuentes

  3. Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, UK

    Narcis Fernández-Fuentes

Authors
  1. Alberto Meseguer
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  2. Patricia Bota
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  3. Narcis Fernández-Fuentes
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  4. Baldo Oliva
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Correspondence to Baldo Oliva .

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Editors and Affiliations

  1. Insilico Medicine Hong Kong Ltd, Pak Shek Kok, Hong Kong

    Quentin Vanhaelen

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Meseguer, A., Bota, P., Fernández-Fuentes, N., Oliva, B. (2022). Prediction of Protein–Protein Binding Affinities from Unbound Protein Structures. In: Vanhaelen, Q. (eds) Computational Methods for Estimating the Kinetic Parameters of Biological Systems. Methods in Molecular Biology, vol 2385. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1767-0_16

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  • DOI: https://doi.org/10.1007/978-1-0716-1767-0_16

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1766-3

  • Online ISBN: 978-1-0716-1767-0

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