Journal of Computer-Aided Molecular Design

, Volume 28, Issue 7, pp 699–710 | Cite as

Ligand efficiency metrics considered harmful

  • Peter W. Kenny
  • Andrei Leitão
  • Carlos A. Montanari


Ligand efficiency metrics are used in drug discovery to normalize biological activity or affinity with respect to physicochemical properties such as lipophilicity and molecular size. This Perspective provides an overview of ligand efficiency metrics and summarizes thermodynamics of protein–ligand binding. Different classes of ligand efficiency metric are critically examined and the study concludes with suggestions for alternative ways to account for physicochemical properties when prioritizing and optimizing leads.


Acid/base properties Ligand efficiency Lipophilic efficiency Metric Property-based design 


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Peter W. Kenny
    • 1
  • Andrei Leitão
    • 1
  • Carlos A. Montanari
    • 1
  1. 1.Grupo de em Química Medicinal do IQSC/USP – NEQUIMED, Instituto de Química de São CarlosUniversidade de São PauloSão CarlosBrazil

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