Debunking the Idea that Ligand Efficiency Indices Are Superior to pIC50 as QSAR Activities

Several papers have appeared in which
a ligand efficiency index
instead of pIC50 is used as the activity in QSAR. The claim is that
better fits and predictions are obtained with ligand efficiency. We
show on both public-domain and in-house data sets that the apparent
superiority is a statistical artifact that occurs when ligand efficiency
indices are correlated with the physical property included in their
definition (number of non-hydrogens, ALOGP, TPSA, etc.) and when the
property is easier to predict than the original pIC50.