Ligand efficiency indices for an effective mapping of chemico-biological space: the concept of an atlas-like representation

Abstract

We propose a numerical framework that permits an effective Atlas-like representation of Chemico-Biological Space (CBS) based on a series of Cartesian planes mapping the ligands with the corresponding targets connected by an affinity parameter (Ki or related). The numerical framework is derived from the concept of ligand efficiency indices (LEIs), which provide a natural coordinate system combining the potency toward the target (biological space) with the physicochemical properties of the ligand (chemical space). This framework facilitates navigation in the multidimensional drug-discovery space using map-like representations based on pairs of combined variables related to the efficiency of the ligands per Dalton (MW or number of non-hydrogen atoms) and per unit of polar surface area (or number of polar atoms).