TY - JOUR
T1 - Allostery and population shift in drug discovery
AU - Kar, Gozde
AU - Keskin, Ozlem
AU - Gursoy, Attila
AU - Nussinov, Ruth
N1 - Funding Information:
This work has been supported by TUBITAK (Research Grant Numbers: 109T343 and 109E207 ). This project has been funded in whole or partly with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (partly) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
PY - 2010/12
Y1 - 2010/12
N2 - Proteins can exist in a large number of conformations around their native states that can be characterized by an energy landscape. The landscape illustrates individual valleys, which are the conformational substates. From the functional standpoint, there are two key points: first, all functionally relevant substates pre-exist; and second, the landscape is dynamic and the relative populations of the substates will change following allosteric events. Allosteric events perturb the structure, and the energetic strain propagates and shifts the population. This can lead to changes in the shapes and properties of target binding sites. Here we present an overview of dynamic conformational ensembles focusing on allosteric events in signaling. We propose that combining equilibrium fluctuation concepts with genomic screens could help drug discovery.
AB - Proteins can exist in a large number of conformations around their native states that can be characterized by an energy landscape. The landscape illustrates individual valleys, which are the conformational substates. From the functional standpoint, there are two key points: first, all functionally relevant substates pre-exist; and second, the landscape is dynamic and the relative populations of the substates will change following allosteric events. Allosteric events perturb the structure, and the energetic strain propagates and shifts the population. This can lead to changes in the shapes and properties of target binding sites. Here we present an overview of dynamic conformational ensembles focusing on allosteric events in signaling. We propose that combining equilibrium fluctuation concepts with genomic screens could help drug discovery.
UR - http://www.scopus.com/inward/record.url?scp=78149473070&partnerID=8YFLogxK
U2 - 10.1016/j.coph.2010.09.002
DO - 10.1016/j.coph.2010.09.002
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AN - SCOPUS:78149473070
SN - 1471-4892
VL - 10
SP - 715
EP - 722
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
IS - 6
ER -