System setup, including the creation of a water box and addition of neutralizing ions, was performed using AmberTools 17 . The majority of simulations were conducted using protein parameters taken from the standard Amber force field for bioorganic systems (ff14SB) . Reproducibility studies of the THQ ligands were conducted using an earlier version of the forcefield, ff99SBildn Drug parameters were produced using the general Amber force field (GAFF) . The majority of the simulations presented here employ ligands prepared using the Gaussian/RESP protocol. In this approach, Gaussian 98 was used to perform geometric optimization of the inhibitor with 6-31G** basis functions, and the restrained electrostatic potential (RESP) procedure was used to calculate the partial atomic charges. Reproducibility studies of the DIV dataset were conducted using AM1-BCC derived charges. All charge assignment and input file generation was performed in the Antechamber component of AmberTools.