Novel Covalent Modifier-Induced Local Conformational Changes within the Intrinsically Disordered Region of the Androgen Receptor.

ABSTRACT: Intrinsically disordered regions (IDRs) of transcription factors play an important biological role in liquid condensate formation and gene regulation. It is thus desirable to investigate the druggability of IDRs and how small-molecule binders can alter their conformational stability. For the androgen receptor (AR), certain covalent ligands induce important changes, such as the neutralization of the condensate. To understand the specificity of ligand-IDR interaction and potential implications for the mechanism of neutralizing liquid-liquid phase separation (LLPS), we modeled and performed computer simulations of ligand-bound peptide segments obtained from the human AR. We analyzed how different covalent ligands affect local secondary structure, protein contact map, and protein-ligand contac

SUBMITTER: Harnish MT 

PROVIDER: S-EPMC10669190 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature