However, if timescales for transition between binding modes are very slow (as is especially the case with MD) this may not be the case on the timescale of any reasonable simulationas we find here. Given that our BLUES approach proposes random rotational moves on the ligand every 200ps, we did not expect the ligand to remain trapped in the crystallographic binding mode like we did with MD. Thus, this highlights that with BLUES, not only are we able to sample the crystal structure but we are able to recover the correct populations-unlike with MD.