Fig. 3.
Conformational analysis of the free enantiomers calculated with the program quanta (Molecular Simulations, San Diego, CA); the torsion angles of the ligands defined at the bottom have been varied by increments of 20°, followed by a short energy minimization after each step. Energy contour plots are depicted for the combination of two torsion angles, with the third chosen closest to the value observed in the structure of the corresponding hRARg LBD complex. The energy scale is in kcal/mol, and the contours are colored from blue (more stable) to red (less stable) for increasing energy values. The black cross marks the torsion angles observed for the bound ligand. BMS270394 exhibits relatively large areas of favorable torsion angles (dark blue), and the values observed in the complex are close to them. BMS270395, however, has very restricted favorable conformations, which cannot be adopted in the complex because of contact restraints within the pocket.