We performed 1000 steps of conjugate gradient minimization and 10 ps of QM/MM equilibration with 0.5 fs time step. Position restraints of 1000 kJ/mol/nm 2 were active on protein heavy atoms in the MM region only. Production time was 20 ps per walker, potential height and width were 0.5 kJ/mol and 0.1Å respectively. Bias factor was set to 10. All other setup and analysis details were the same as above.