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Investigating Conformational Dynamics and Allostery in the p53 DNA-Binding Domain Using Molecular Simulations

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Allostery

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

Abstract

The p53 tumor suppressor is a multifaceted context-dependent protein, which is involved in multiple cellular pathways, with the ability to either keep the cells alive or to kill them through mechanisms such as apoptosis. To complicate this picture, cancer cells that express mutant p53 becomes addicted to the mutant activity, so that the mutant variant features a myriad of gain-of-function activities, opening different venues for therapy. This makes essential to think outside the box and apply new approaches to the study of p53 structure–(mis)function relationship to find new critical components of its pathway or to understand how known parts are interconnected, compete, or cooperate. In this context, I will here illustrate how to integrate different computational methods to the identification of possible allosteric effects transmitted from the DNA binding interface of p53 to regions for cofactor recruitment. The protocol can be extended to any other cases of study. Indeed, it does not necessarily apply only to the study of DNA-induced effects, but more broadly to the investigation of long-range effects induced by a biological partner that binds to a biomolecule of interest.

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Acknowledgements

This work was supported by the ISCRA-CINECA HPC Grants (HP10BLFPW4 and HP10C8LO8N) and the EU-PRACE DECI project DyNet. I would like to thank Matteo Lambrughi for fruitful inputs in the writing of this protocol.

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  1. Computational Biology Laboratory, Danish Cancer Society Research Center, Copenhagen, Denmark

    Elena Papaleo

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  1. Elena Papaleo
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Correspondence to Elena Papaleo .

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  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

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Papaleo, E. (2021). Investigating Conformational Dynamics and Allostery in the p53 DNA-Binding Domain Using Molecular Simulations. 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_13

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  • DOI: https://doi.org/10.1007/978-1-0716-1154-8_13

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1153-1

  • Online ISBN: 978-1-0716-1154-8

  • eBook Packages: Springer Protocols

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