Allosteric Binding Sites On Nuclear Receptors: Focus On Drug Efficacy and Selectivity.

ABSTRACT: Nuclear receptors (NRs) are highly relevant drug targets in major indications such as oncologic, metabolic, reproductive, and immunologic diseases. However, currently, marketed drugs designed towards the orthosteric binding site of NRs often suffer from resistance mechanisms and poor selectivity. The identification of two superficial allosteric sites, activation function-2 (AF-2) and binding function-3 (BF-3), as novel drug targets sparked the development of inhibitors, while selectivity concerns due to a high conservation degree remained. To determine important pharmacophores and hydration sites among AF-2 and BF-3 of eight hormonal NRs, we systematically analyzed over 10 μ s of molecular dynamics simulations including simulations in explicit water and solvent mixtures. In addition, a lib

SUBMITTER: Fischer A 

PROVIDER: S-EPMC7014104 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature