Figure 16.

Example of cooperativity between two ligand hydroxyl groups in a Hsp90 inhibitor series.(79) Replacing the 4-OH group (O22) with 2-OH (O19) leads to a significant reduction in ligand efficiency, while having both 2-OH and 4-OH substitutions results in a significant gain in ligand efficiency. The “cp pairs” list gives the computed cooperative pairs, and the atom labels in the binding site view denote the atoms involved. Two LPL_l paths of a length of 4 connecting the two hydroxyl groups involved in cooperativity are displayed (PDB code 2xab).