Simple size-independent measure of ligand efficiency

Abstract

This paper suggests a functional form for a size-independent ligand efficiency (LE) measure of the form SILE = affinity/N(0.3), where N is the number of heavy atoms. The size-dependency effect of the commonly used LE measure (LE = affinity/N) is apparent in experimental settings like hit-to-lead optimization, but equally well applies to in-silico binding-energy-based estimates. It is therefore expected that the correction is useful in experimental drug optimization, as well as in in-silico applications like protein-ligand docking.