title: Allostery and population shift in drug discovery.
abstract: 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.
authors.affiliation: Center for Computational Biology and Bioinformatics and College of Engineering, Koc University Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey.
authors.forename: Gozde
authors.initials: G
authors.lastname: Kar
authors.forename: Ozlem
authors.initials: O
authors.lastname: Keskin
authors.forename: Attila
authors.initials: A
authors.lastname: Gursoy
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D000494:Allosteric Regulation; D001665:Binding Sites; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins