EPFL Logo
fr|en
Login
Concept

Ligand efficiency

Ligand efficiency is a measurement of the binding energy per atom of a ligand to its binding partner, such as a receptor or enzyme. Ligand efficiency is used in drug discovery research programs to assist in narrowing focus to lead compounds with optimal combinations of physicochemical properties and pharmacological properties. Mathematically, ligand efficiency (LE) can be defined as the ratio of Gibbs free energy (ΔG) to the number of non-hydrogen atoms of the compound: LE = -(ΔG)/N where ΔG = −RTlnKi and N is the number of non-hydrogen atoms. It can be transformed to the equation: LE = 1.4(−log IC50)/N Some suggest that better metrics for ligand efficiency are percentage/potency efficiency index (PEI), binding efficiency index (BEI) and surface-binding efficiency index (SEI) because they are easier to calculate and take into account the differences between elements in different rows of the periodic table. It is important to note that PEI is a relative measure for comparing compounds tested in the same conditions (e.g. a single-point assay) and are not comparable at different inhibitor concentrations. Also for BEI and SEI, similar measurements must be used (e.g. always using pKi). PEI = (% inhibition at a given compound concentration as fraction: 0 – 1.0) / (molecular weight, kDa) BEI = (pKi, pKd, or pIC50) / (molecular weight, kDa) SEI = (pKi, pKd, or pIC50) / (PSA/100 Å) where pKi, pKd and pIC50 is defined as −log(Ki), −log(Kd), or −log(IC 50), respectively. Ki and IC50 in mol/L. The authors suggest plotting compounds SEI and BEI on a plane and optimizing compounds towards the diagonal and so optimizing both SEI and BEI which incorporate potency, molecular weight and PSA. There are other metrics which can be useful during hit to lead optimization: group efficiency (GE), lipophilic efficiency/lipophilic ligand efficiency (LipE/LLE), ligand lipophilicity index (LLEAT) ligand efficiency dependent lipophilicity (LELP), fit quality scaled ligand efficiency (LEscale), size independent ligand efficiency (SILE).

Official source
About this result
This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.
Related courses (3)
BIO-478: Pharmacology and pharmacokinetics
This course introduces the student to the fudamentals of pharmacology, pharmacokinetics and drug-receptor interactions. It discusses also pharmacogenetics and chronopharmacology, to exemplify the chal
EE-515: Fundamentals of biosensors and electronic biochips
The labels "biosensor"€ and "eBiochip" have been employed to refer to the most diverse systems and in several fields of application. The course is meant not only to provide means to dig into this sea
BIO-212: Biological chemistry I
Biochemistry is a key discipline for the Life Sciences. Biological Chemistry I and II are two tightly interconnected courses that aim to describe and understand in molecular terms the processes that m
Related publications (28)
Show more
Related people (3)
Related concepts (3)
Hit to lead
Hit to lead (H2L) also known as lead generation is a stage in early drug discovery where small molecule hits from a high throughput screen (HTS) are evaluated and undergo limited optimization to identify promising lead compounds. These lead compounds undergo more extensive optimization in a subsequent step of drug discovery called lead optimization (LO).
Drug design
Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it.
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by serendipitous discovery, as with penicillin. More recently, chemical libraries of synthetic small molecules, natural products or extracts were screened in intact cells or whole organisms to identify substances that had a desirable therapeutic effect in a process known as classical pharmacology.

Copyright © 2025 EPFL, all rights reserved

Graph Chatbot

Chat with Graph Search

Ask any question about EPFL courses, lectures, exercises, research, news, etc. or try the example questions below.

DISCLAIMER: The Graph Chatbot is not programmed to provide explicit or categorical answers to your questions. Rather, it transforms your questions into API requests that are distributed across the various IT services officially administered by EPFL. Its purpose is solely to collect and recommend relevant references to content that you can explore to help you answer your questions.