The structures of Hsp90α and β (PDB IDs 3q6m and 5fwk respectively) were prepared using Schrödinger Maestro 80 . For each of the isoforms, 40 individual MD simulations were performed. Initial random placement of 5b and solvation in TIP3P water was done using PACKMOL , neutralizing the system by the addition of sodium ions. ff14SB was used as force field for the protein and a modified GAFF version 1.5 for 5b. All simulations were carried out using the Amber18 software package. To treat long-range electrostatics, the particle mesh Ewald method was used with a cutoff of 9.0 Å for equilibration and 10.0 Å for production. The SHAKE algorithm and hydrogen mass repartitioning were used to allow for simulation steps of 2 fs in the equilibration and 4 fs in the production.