Title:Molecular Property Filters Describing Pharmacokinetics and Drug Binding
Volume: 19
Issue: 11
Author(s): A. T. Garcia-Sosa, U. Maran and C. Hetenyi
Affiliation:
Keywords:
Binding site, entropy, free energy, molecule, pocket, protein, structure, target, logP, Wiener index
Abstract: Drug-target binding affinity and pharmacokinetics are equally important factors of drug design. Simple molecular properties
such as molecular size have been used as pharmacokinetic and/or drug-likeness filters during chemical library design and also correlated
with binding affinity. In the present study, current property filters are reviewed, a collection of their optimal values is provided, and a
statistical framework is introduced allowing calibration of their selectivity and sensitivity for drugs. The role of ligand efficiency indices
in drug design is also described. It is concluded that the usefulness of property filters of molecular size and lipophilicity is limited as
predictors of general drug-likeness. However, they demonstrate increased performance in specific cases, e.g. in central nervous system
diseases, emphasizing their future importance in specific, disease-focused library design instead of general drug-likeness filtering.
