Ligand efficiency

Ligand efficiency is a measurement of the binding energy per atom of a ligand to its binding partner, such as a receptor or enzyme.[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:

LE = -(ΔG)/N

where ΔG = −RTlnKi and N is the number of non-hydrogen atoms.[3] It can be transformed to the equation:[4]

LE = 1.4(−log IC50)/N
  1. ^ Kuntz ID, Chen K, Sharp KA, Kollman PA (August 1999). "The maximal affinity of ligands". Proceedings of the National Academy of Sciences of the United States of America. 96 (18): 9997–10002. Bibcode:1999PNAS...96.9997K. doi:10.1073/pnas.96.18.9997. PMC 17830. PMID 10468550.
  2. ^ Abad-Zapatero C, Metz JT (April 2005). "Ligand efficiency indices as guideposts for drug discovery". Drug Discovery Today. 10 (7): 464–469. doi:10.1016/S1359-6446(05)03386-6. PMID 15809192.
  3. ^ Hopkins AL, Groom CR, Alex A (May 2004). "Ligand efficiency: a useful metric for lead selection". Drug Discovery Today. 9 (10): 430–431. doi:10.1016/S1359-6446(04)03069-7. PMID 15109945.
  4. ^ Cite error: The named reference Shultz was invoked but never defined (see the help page).