While mutations in R288 and R357 have been linkedto impaired PPARγ function associated with metabolic disordersand cancer,27 our study offers the firstcomprehensive characterization of their cooperative roles alongsideE295, R280, E276, and E460 in regulating PPARγ-LBD dynamics.Both cMD and GaMD simulations revealed significant stability of H12,even in the apo forms, maintaining the ligand-induced conformationwithout drastic helix shifts. The gene discussed is PPARG; the disease is cancer.