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Modeling Macromolecular Complexes: A Journey Across Scales

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Modeling in Computational Biology and Biomedicine

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Abstract

While proteins and nucleic acids are the fundamental components of an organism, Biology itself is based on the interactions they make with each other. Analyzing macromolecular interactions typically requires handling systems involving from two to hundreds of polypeptide chains. After a brief overview of the modeling challenges faced in computational structural biology, this chapter presents concepts and tools aiming at improving our understanding of the link between the static structures of macromolecular complexes and their biophysical/biological properties. We discuss geometrical approaches suited to atomic-resolution complexes and to large protein assemblies; for each, we also present examples of their successful application in quantifying and interpreting biological data. This methodology includes state-of-the-art geometric analyses of surface area, volume, curvature, and topological properties (isolated components, cavities, voids, cycles) related to Voronoï constructions in the context of structure analysis. On the applied side, we present novel insights into real biological problems gained thanks to these modeling tools.

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Notes

  1. 1.

    While single-chain proteins are common, one protein may include more than one polypeptide chain. Multiple chains are frequently covalently bonded via a disulfide bond formed between cysteine residues.

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Acknowledgements

Joël Janin is acknowledged for insightful discussions.

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Authors and Affiliations

  1. Inria Sophia Antipolis Méditerranée, ABS project-team, 2004 Route des Lucioles, 06902, Sophia Antipolis, France

    Frédéric Cazals & Tom Dreyfus

  2. Laboratoire de Biochimie Théorique – UPR 9080 CNRS, Institut de Biologie Physico Chimique, Université Paris Diderot Sorbonne Paris Cité, 13 rue Pierre et Marie Curie, 75005, Paris, France

    Charles H. Robert

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  1. Frédéric Cazals
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Correspondence to Frédéric Cazals .

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  1. , Algorithms-Biology-Structure, INRIA Sophia Antipolis - Méditerranée, Route des Lucioles 2004, Sophia Antipolis, 06902, France

    Frédéric Cazals

  2. , NeuroMathComp project team, INRIA Sophia Antipolis - Méditerranée, Route des Lucioles 2004, Sophia Antipolis, 06902, France

    Pierre Kornprobst

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Cazals, F., Dreyfus, T., Robert, C.H. (2013). Modeling Macromolecular Complexes: A Journey Across Scales. In: Cazals, F., Kornprobst, P. (eds) Modeling in Computational Biology and Biomedicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-31208-3_1

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