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. © 2012 by the authors; licensee MDPI, Basel, Switzerland.
Molecular dynamics simulations of Hsp90 with an eye to inhibitor design
colombo g
2012-01-01
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. © 2012 by the authors; licensee MDPI, Basel, Switzerland.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
