[1] Ligand efficiency is used in drug discovery research programs to assist in narrowing focus to lead compounds with optimal combinations of physicochemical properties and pharmacological properties.
[2] Mathematically, ligand efficiency (LE) can be defined as the ratio of Gibbs free energy (ΔG) to the number of non-hydrogen atoms of the compound: where ΔG = −RTlnKi and N is the number of non-hydrogen atoms.
It is important to note that PEI is a relative measure for comparing compounds tested in the same conditions (e.g. a single-point assay) and are not comparable at different inhibitor concentrations.
The authors suggest plotting compounds SEI and BEI on a plane and optimizing compounds towards the diagonal and so optimizing both SEI and BEI which incorporate potency, molecular weight and PSA.
[5] Unlike ligand efficiency which evaluates the efficiency of the entire molecule, group efficiency measures the relative change of the Gibbs free energy (ΔΔG), caused by addition or modification of groups, normalized by the change in the number heavy atoms in those groups (ΔN), using the equation: