Ligand efficiency

Ligand efficiency (LE) represents the relationship between target binding and the number of heavy atoms (non-hydrogen atoms) in a molecule.

Compounds with a better binding affinity (eg IC₅₀) for a given size (in terms of number of non-hydrogen atoms) are more ligand efficient.

Ligand efficiency is used in drug discovery research programs to assist in choosing compounds with optimal combinations of physicochemical and pharmacological properties. Ligand efficiency is particularly used in fragment-based screening, where small molecules (fragments) are evaluated as building blocks towards a potential drug molecule.  Fragments with higher LE values are considered to offer greater opportunity for further elaboration.

The full definition of Ligand Efficiency is

LE (binding energy in kcal/mol per heavy atom) = pXC₅₀ × 1.37/heavy atom count (HAC)

XC₅₀ refers to the negative logarithm of the binding affinity in molar concentration, which can be measured as either EC₅₀ or IC_50.

The EC₅₀ is the concentration of a molecule that gives half-maximal response. The IC₅₀ is the concentration of an inhibitor where the response (or binding) is reduced by half.