We then set out to study if there is an isoform specificity for the binding of 5b because the helical interface regions differ in three positions: α: S641, β: P633; α: S658, β: A650; α: A685, β: S677 (SI Figure ). Using the same setup as before, we performed MD simulations of free ligand diffusion around Hsp90β. The probability density of bound 5b again revealed that the C-terminal helix interface is the most preferred region, followed by the cleft between the CTD and middle domain (SI Figure ).