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Pharmaceuticals 2012, 5(9), 944-962; doi:10.3390/ph5090944
Review

Molecular Dynamics Simulations of Hsp90 with an Eye to Inhibitor Design

,
 and
*
Institute of Molecular Recognition Chemistry, CNR, via Mario Bianco 9, 20131 Milano, Italy
* Author to whom correspondence should be addressed.
Received: 5 July 2012 / Revised: 28 August 2012 / Accepted: 31 August 2012 / Published: 10 September 2012
(This article belongs to the Special Issue Hsp90 Inhibitors)
View Full-Text   |   Download PDF [903 KB, 11 September 2012; original version 10 September 2012]   |   Browse Figures

Abstract

Proteins carry out their functions through interactions with different partners. Dynamic conformational switching among different structural sub-states favors the adaptation to the shapes of the different partners. Such conformational changes can be determined by diverse biochemical factors, such as ligand-binding. Atomic level investigations of the mechanisms that underlie functional dynamics may provide new opportunities for the discovery of leads that target disease-related proteins. In this review, we report our views and approaches on the development of novel and accurate physical-chemistry-based models for the characterization of the salient aspects of the ligand-regulated dynamics of Hsp90, and on the exploitation of such new knowledge for the rational discovery of inhibitors of the chaperone.
Keywords: drug design; dynamic drug discovery; Hsp90; inhibitors; allostery; binding; molecular dynamics; simulations drug design; dynamic drug discovery; Hsp90; inhibitors; allostery; binding; molecular dynamics; simulations
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Moroni, E.; Morra, G.; Colombo, G. Molecular Dynamics Simulations of Hsp90 with an Eye to Inhibitor Design. Pharmaceuticals 2012, 5, 944-962.

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