τRandom Accelerated Molecular Dynamics. The protocol to perform the τRAMD simulations was reproduced from Kokh et al.. All HSP90α ligands were tested, while only testing the ligand of the PDB entry 2QZL for BACE-1 and 10 CDK2 inhibitors (CHEMBL409731, CHEMBL1234085, CHEMBL112136, CHEMBL333382, CHEMBL411426, CHEMBL271842, CHEMBL419534, CHEMBL316809, as well as PDB entries 2R3K and 2C68). Using the whole (non-chunked) receptors, the systems were solvated in truncated octahedral TIP3P boxes with sodium chlorines added to obtain charge neutrality. GAFF and ff14SB were used for the atom types and parameters for the ligands and proteins, respectively. The partial charges of the HSP90α ligands were provided by D. Kokh. They had been calculated via the RESP procedure from ab initio calculations at the Hartree-Fock level with the 6-31G*(1d) basis set in GAMESS. The parameters for the HSP90α and BACE1 ligands were obtained from the DUck preparation (i.e., SMIRNOFF99 PFrosst force field and AM1-BCC derived partial charges). The systems were minimized in AMBER16 with 500 steps of steepest descent and 1000 steps of conjugate gradient. They were then gradually heated to 300 K in 1 ns using harmonic restraints on the heavy atoms with a force constant of 50 kcal mol -1