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Molecular Dynamics Simulations in Protein–Protein Docking

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Protein-Protein Docking

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2780))

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Abstract

Concerted interactions between all the cell components form the basis of biological processes. Protein–protein interactions (PPIs) constitute a tremendous part of this interaction network. Deeper insight into PPIs can help us better understand numerous diseases and lead to the development of new diagnostic and therapeutic strategies. PPI interfaces, until recently, were considered undruggable. However, it is now believed that the interfaces contain “hot spots,” which could be targeted by small molecules. Such a strategy would require high-quality structural data of PPIs, which are difficult to obtain experimentally. Therefore, in silico modeling can complement or be an alternative to in vitro approaches. There are several computational methods for analyzing the structural data of the binding partners and modeling of the protein–protein dimer/oligomer structure. The major problem with in silico structure prediction of protein assemblies is obtaining sufficient sampling of protein dynamics. One of the methods that can take protein flexibility and the effects of the environment into account is Molecular Dynamics (MD). While sampling of the whole protein–protein association process with plain MD would be computationally expensive, there are several strategies to harness the method to PPI studies while maintaining reasonable use of resources. This chapter reviews known applications of MD in the PPI investigation workflows.

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Acknowledgments

The work was supported by the Polish National Agency for Academic Exchange within the Bekker NAWA Programme, project PANALLOS, grant number BPN/BEK/2021/1/00408/U/00001.

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Authors and Affiliations

  1. Laboratory of Plant Protein Phosphorylation, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland

    Dominika Cieślak

  2. Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden

    Ivo Kabelka & Damian Bartuzi

  3. Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modelling Lab, Medical University of Lublin, Lublin, Poland

    Damian Bartuzi

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  1. Dominika Cieślak
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  2. Ivo Kabelka
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  3. Damian Bartuzi
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Correspondence to Damian Bartuzi .

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  1. Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland

    Agnieszka A. Kaczor

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Cieślak, D., Kabelka, I., Bartuzi, D. (2024). Molecular Dynamics Simulations in Protein–Protein Docking. In: Kaczor, A.A. (eds) Protein-Protein Docking. Methods in Molecular Biology, vol 2780. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3985-6_6

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