Ligand Efficiency Indices (LEIs): More than a Simple Efficiency Yardstick.

Abstract

The concept of ligand efficiency and the usage of ligand efficiency values to assess the quality of fragments and compounds is becoming more accepted in the practice of medicinal chemistry. This is particularly true as it refers to the efficiency of ligands per unit size (i.e., binding affinity/number of non-hydrogen atoms or binding affinity/MW). The use of the Ligand Efficiency Indices (LEIs) as variables for a Cartesian mapping of chemico-biological space, the concept of AtlasCBS, has been presented in a recent publication with some initial drug-discovery applications. In this communication, we present additional applications of the concept in three domains of drug discovery: i) analyze and compare the content of databases: inhibitors vs. drugs; ii) polypharmacology; and iii) applications to Fragment-Based strategies. We suggest that the combined use of LEIs in a Cartesian representation of Chemico-Biological Space (AtlasCBS) could be a useful tool in various aspects of drug-discovery in the future.