All ligand pairs (data yet to be published). It is evident that one could never understand the behaviour of these ensembles by only running 1-3 replicas. We found that the distribution of experimental binding free energies obtained from a limited number of selected ligands which have been subjected to many repeated measurements over a lengthy period are also non-Gaussian. The underlying implication of non-normal statistics is that more frequent occurrence of outliers mean larger error bars and that graphs comparing predicted and experimental predictions will deviate from ideal linear plots with all points lying close to a straight line with slope 1. This needs to be borne in mind when interpreting the resultant correlation plots. Statistical tools like bootstrapping and linear regression should still, in principle, be applicable. However, their quantitative reliability for non-normal distributions is questionable for small sample size as the law of large numbers is not then applicable.