After the thermalization, 500 ns of NPT MD simulations were carried out with positional restraints with a force constant of 0.1 kcal mol -1 Å -2 on the backbone atoms. The Langevin thermostat with a collision frequency of 1 ps -1 and the Monte Carlo barostat with a pressure relaxation time of 1 ps were used. The reference coordinates for these restraints were readjusted every 100 ns to allow for moderate protein flexibility. For Hsp90α, these simulations were later extended to 1 µs. The trajectories were postprocessed and analyzed with CPPTRAJ , and results were visualized with PyMol .