Allostery and population shift in drug discovery

摘要: Proteins can exist in a large number of conformations around their native states that be characterized by an energy landscape. The landscape illustrates individual valleys, which are the conformational substates. From functional standpoint, there two key points: first, all functionally relevant substates pre-exist; and second, is dynamic relative populations will change following allosteric events. Allosteric events perturb structure, energetic strain propagates shifts population. This lead to changes shapes properties target binding sites. Here we present overview ensembles focusing on signaling. We propose combining equilibrium fluctuation concepts with genomic screens could help drug discovery.