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Tyrosine kinases: complex molecular systems challenging computational methodologies

  • Topical Review - Computational Methods
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Abstract

Classical molecular dynamics (MD) simulations based on atomic models play an increasingly important role in a wide range of applications in physics, biology, and chemistry. Nonetheless, generating genuine knowledge about biological systems using MD simulations remains challenging. Protein tyrosine kinases are important cellular signaling enzymes that regulate cell growth, proliferation, metabolism, differentiation, and migration. Due to the large conformational changes and long timescales involved in their function, these kinases present particularly challenging problems to modern computational and theoretical frameworks aimed at elucidating the dynamics of complex biomolecular systems. Markov state models have achieved limited success in tackling the broader conformational ensemble and biased methods are often employed to examine specific long timescale events. Recent advances in machine learning continue to push the limitations of current methodologies and provide notable improvements when integrated with the existing frameworks. A broad perspective is drawn from a critical review of recent studies.

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Data Availability Statement

This manuscript has no associated data or the data will not be deposited. [Authors’ comment: This is a review, therefore no data was deposited.]

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Acknowledgements

This work is supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) through grant R01-CAO93577.

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  1. Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, 60637, USA

    Trayder Thomas & Benoît Roux

  2. Gordon Center for Integrative Science, 929 E 57th Street, Room W323B, Chicago, IL, 60637, USA

    Trayder Thomas & Benoît Roux

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TT and BR wrote the paper.

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Thomas, T., Roux, B. Tyrosine kinases: complex molecular systems challenging computational methodologies. Eur. Phys. J. B 94, 203 (2021). https://doi.org/10.1140/epjb/s10051-021-00207-7

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