Unravelling the structural impact of progesterone receptor mutations in myoma and progesterone intolerance through computational modeling

• Description :

  This study investigates the structural and functional impact of missense mutations in the progesterone receptor encoded by the PGR, which mediates the actions of the steroid hormone Progesterone in female reproductive physiology. Computational and structural bioinformatics analyses identified 11 deleterious variants within the ligand-binding domain that destabilize receptor structure and impair co-activator interactions, despite minimal effects on progesterone binding. Ensemble and protein–peptide docking revealed that disrupted co-activator binding—critical for progesterone signaling—may underlie disease mechanisms. Notably, variants R869H and C798Y were predicted to contribute to myoma and progesterone tolerance, respectively, providing mechanistic insight and a foundation for targeted therapeutic strategies in PR-associated reproductive disorders.