Journal
CURRENT OPINION IN PHARMACOLOGY
Volume 10, Issue 6, Pages 715-722Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.coph.2010.09.002
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Funding
- TUBITAK [109T343, 109E207]
- National Cancer Institute National Institutes of Health [HHSN261200800001E]
- NIH National Cancer Institute Center for Cancer Research
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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
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