Allostery and population shift in drug discovery

Gozde Kar, Ozlem Keskin, Attila Gursoy, Ruth Nussinov*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Pages (from-to)715-722
Number of pages8
JournalCurrent Opinion in Pharmacology
Issue number6
StatePublished - Dec 2010


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