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Computational Modeling of the Hsp90 Interactions with Cochaperones and Small-Molecule Inhibitors

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Chaperones

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1709))

Abstract

Allosteric interactions of the molecular chaperone Hsp90 with a diverse array of cochaperones and client proteins, such as protein kinases and transcription factors, allow for efficient molecular communication in signal transduction networks. Deregulation of pathways involving these proteins is commonly associated with cancer pathologies and allosteric inhibition of oncogenic clients by targeting Hsp90 provides a powerful therapeutic strategy in cancer research. We review several validated computational approaches and tools used in the studies of the Hsp90 interactions with proteins and small molecules. These methods include experimentally guided docking to predict Hs90-protein interactions, molecular and binding free energy simulations to analyze Hsp90 binding with small molecules, and structure-based network modeling to evaluate allosteric interactions and communications in the Hsp90 regulatory complexes. Through the lens of allosteric-centric view on Hsp90 function and regulation, we discuss newly emerging computational tools that link protein structure modeling with biophysical simulations and network-based systems biology approaches.

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Authors and Affiliations

  1. Schmid College of Science and Technology, Chapman University, University Drive, Orange, CA, 92866, USA

    Gennady M. Verkhivker

  2. Chapman University School of Pharmacy, Irvine, CA, USA

    Gennady M. Verkhivker

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  1. Gennady M. Verkhivker
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Correspondence to Gennady M. Verkhivker .

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Editors and Affiliations

  1. Department of Radiation, Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Stuart K. Calderwood

  2. Department of Urology, Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, USA

    Thomas L. Prince

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Verkhivker, G.M. (2018). Computational Modeling of the Hsp90 Interactions with Cochaperones and Small-Molecule Inhibitors. In: Calderwood, S., Prince, T. (eds) Chaperones. Methods in Molecular Biology, vol 1709. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7477-1_19

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  • DOI: https://doi.org/10.1007/978-1-4939-7477-1_19

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