Covalent adducts formed by the androgen receptor transactivation domain and small molecule drugs remain disordered.

ABSTRACT: Intrinsically disordered proteins are implicated in many human diseases. Small molecules that target the disordered androgen receptor transactivation domain have entered human trials for the treatment of castration-resistant prostate cancer. These molecules have been shown to react with cysteine residues of the androgen receptor transactivation domain and form covalent adducts under physiological conditions. It is currently unclear how covalent attachment of these molecules alters the conformational ensemble of the androgen receptor. Here, we utilize all-atom molecular dynamics computer simulations to simulate covalent adducts of the small molecule ligands EPI-002 and EPI-7170 bound to the disordered androgen receptor transactivation domain. Our simulations reveal that the conformational e

SUBMITTER: Zhu J 

PROVIDER: S-EPMC11601358 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature