Lennard-Jones interactions have been truncated at 12 Å, beyond which a continuum-model dispersion correction is applied. All bonds are constrained by the SHAKE algorithm. A multiple time-step integration scheme is implemented to integrate the equation of motion. A time-step of 0.5 fs is used for bonds and angles respectively, whereas 1.5 fs is used for torsions and non-bonded interactions up to a distance of 7 Å. Finally, for non-bonded interactions above 7 Å a time-step of 3 fs is used, and also same time-step is used for the reciprocal part of the Ewald summation.