title: Ligand efficiency metrics considered harmful.
abstract: 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.
authors.affiliation: Grupo de em Química Medicinal do IQSC/USP - NEQUIMED, Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador Sancarlense, 400, São Carlos, SP, 13566-590, Brazil, pwk.pub.2008@gmail.com.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kenny
authors.forename: Andrei
authors.initials: A
authors.lastname: Leitão
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Montanari
mesh_terms: D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins