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Ligand efficiency metrics considered harmful

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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.

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Acknowledgments

We are grateful to the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, (Grants #2011/01893-3 and #2011/20572-3) and the Conselho Nacional de Pesquisa (CNPq) for financial support. We thank Peter Bernstein, Anna Linusson and the reviewers of the manuscript for their helpful and constructive advice.

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Correspondence to Peter W. Kenny.

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Kenny, P.W., Leitão, A. & Montanari, C.A. Ligand efficiency metrics considered harmful. J Comput Aided Mol Des 28, 699–710 (2014). https://doi.org/10.1007/s10822-014-9757-8

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  • DOI: https://doi.org/10.1007/s10822-014-9757-8

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