Ligand Efficiency Metrics

Equation (2.1) was derived to provide LE units of kcal/heavy atom. Most often, the correction factor (1.37) in equation (2.1) is not used, and instead of 

In equations (2.3) and (2.4), HA is the heavy atom count. However, LE = affinity HA, being very simple to calculate, is the most widely used measure. 

Lipophilic ligand efficiency (LLE) is a more recent concept than LE and has been implicated in toxicity resulting from promiscuous receptor interactions, which are driven mainly by lipophilicity. It was proposed that LLE values of 

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Rees, D.C., and Reynolds, C.H. (2014) The role of ligand efficiency metrics in drug discovery. Nature Reviews Drug Discovery,... 

Table 16.2 Overview of various ligand efficiency metrics and their typical target range.

Hopkins, A. L., Groom, C. R., and Alex, A. (2004). Ligand efficiency A useful metric for lead selection. Drug Disc. Today 9 430-431. 

A.L. Hopkins, C.R. Groom, and A. Alex, Ligand efficiency a useful metric for lead selection, Drug Discov. Today, 9, 430-431 (2004). 

It is important to point out that when examining small fragments and trying to prioritize them, scientists will often utilize simple metrics such as binding efficiency index (BEI)[3] and ligand efficiency (LE).141 The BEI is calculated using the equation... 

Binding or ligand efficiency (LE) metrics (31), in which the activity is normalized by the molecular size, have been introduced to prioritize screening hits. It has been observed by Hajduk (32) that, during the optimization of a chemical... 

Probably the most widely used metric is called ligand efficiency, or LE. It was first proposed as a brief letter in Drug Discovery Today by Andrew Hopkins and coworkers [78] ... 

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