Chaperones pp 253-273 | Cite as

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

  • Gennady M. VerkhivkerEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1709)


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.

Key words

Hsp90 chaperone Cochaperones Protein client interactions Experimentally guided protein docking Drug discovery Small-molecule inhibitors Protein-ligand interactions Binding free energy simulations Protein structure network analysis Systems biology 


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© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  1. 1.Schmid College of Science and TechnologyChapman UniversityOrangeUSA
  2. 2.Chapman University School of PharmacyCAUSA

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