Discovery of multiple hidden allosteric sites by combining Markov state models and experiments.

ABSTRACT: The discovery of drug-like molecules that bind pockets in proteins that are not present in crystallographic structures yet exert allosteric control over activity has generated great interest in designing pharmaceuticals that exploit allosteric effects. However, there have only been a small number of successes, so the therapeutic potential of these pockets--called hidden allosteric sites--remains unclear. One challenge for assessing their utility is that rational drug design approaches require foreknowledge of the target site, but most hidden allosteric sites are only discovered when a small molecule is found to stabilize them. We present a means of decoupling the identification of hidden allosteric sites from the discovery of drugs that bind them by drawing on new developments in Markov st

SUBMITTER: Bowman GR 

PROVIDER: S-EPMC4352775 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature