An energy minimization was performed with the conjugate gradient algorithm as implemented in GROMACS 5.1.4. The Amber96 forcefield was used for the proteins and the GAFF forcefield was applied via ACPYPE (AnteChamber PYthon Parser inter-facE) to the ligands. In the minimization all heavy atoms were frozen and only the hydrogen atoms were allowed to move. The PDB structures of conformers of 4A4E