Indeed, it is essential to perform ensembles in all cases to quantify the uncertainty and ensure reproducibility of results. This is due to the mixing nature of the dynamics which is a necessary and sufficient condition to reach equilibrium. We would like to note here that the extent of uncertainty (and hence the appropriate size of ensembles) depends on the free energy landscape. For small and/or rigid systems, uncertainties would be much smaller as compared to large and complex protein-ligand systems.