The system was then minimized using sander from AMBER14 with steepest descents running for 20,000 timesteps of 2 fs each and heated from 100K to 300K with constant volume for 25000 timesteps of 2fs. Equilibration continued using sander for 500,000 timesteps of 2 fs under constant pressure with positional restraints initially applied on all non-water atoms at 50 kcal/mol/Å 2 and progressively lifted in increments of 5 kcal/mol/Å 2 over ten 50,000 step segments. The resulting topology and coordinate files of T4 lysozyme with p-xylene bound were used as inputs for MD and BLUES runs.