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Validity of ligand efficiency metrics
Christopher W Murray1, Daniel A Erlanson2, Andrew L Hopkins3
1Astex Pharmaceuticals , 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, U.K.
ACS Medicinal Chemistry Letters
|June 20, 2014
Summary
Ligand efficiency (LE) is mathematically valid, contrary to recent claims. This metric, along with lipophilic ligand efficiency (LLE), remains valuable for medicinal chemists in drug optimization.
Area of Science:
- Medicinal Chemistry
- Computational Chemistry
Background:
- A recent viewpoint questioned the mathematical validity of the standard definition of ligand efficiency (LE).
- Ligand efficiency is a critical metric in drug discovery for evaluating molecular properties.
Purpose of the Study:
- To address and refute the criticism regarding the mathematical validity of ligand efficiency.
- To reaffirm the utility of ligand efficiency and related metrics in medicinal chemistry.
Main Methods:
- Mathematical analysis of the standard definition of ligand efficiency.
- Review and discussion of the application of ligand efficiency in multiparameter optimization.
Main Results:
- The mathematical definition of ligand efficiency (LE) is categorically valid.
- Metrics like LE and lipophilic ligand efficiency (LLE) are confirmed as useful tools.
Conclusions:
- The criticism of ligand efficiency's mathematical validity is unfounded.
- Ligand efficiency and lipophilic ligand efficiency remain important for multiparameter optimization in drug discovery.
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