A novel heuristic of rigid docking scores positively correlates with full-length nuclear receptor LRH-1 regulation.

ABSTRACT: The nuclear receptor Liver Receptor Homolog-1 (LRH-1, NR5A2) is a ligand-regulated transcription factor and validated drug target for several human diseases. LRH-1 activation is regulated by small molecule ligands, which bind to the ligand binding domain (LBD) within the full-length LRH-1. We recently identified 57 compounds that bind LRH-1, and unexpectedly found these compounds regulated either the isolated LBD, or the full-length LRH-1 in cells, with little overlap. Here, we correlated compound binding energy from a single rigid-body scoring function with full-length LRH-1 activity in cells. Although docking scores of the 57 hit compounds did not correlate with LRH-1 regulation in wet lab assays, a subset of the compounds had large differences in binding energy docked to the isol

SUBMITTER: Haratipour Z 

PROVIDER: S-EPMC11342790 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature