ligand efficiency

Ligand efficiency measures how much binding power a molecule gets for its size, like fuel economy for drugs. Two compounds might bind a target equally well, but if one does it with half the atoms, it is the more efficient binder and usually the better starting point.

Formally it is the binding free energy divided by the number of heavy (non-hydrogen) atoms, so it rewards small molecules that punch above their weight. A potent compound bloated with extra atoms that add little binding scores poorly, while a tiny fragment making a few excellent contacts can score very well. This is why fragment-based discovery leans heavily on the metric.

Tracking ligand efficiency, rather than raw potency alone, helps a project add atoms only where they earn their keep and avoid drifting into oversized, greasy molecules. Related measures such as lipophilic ligand efficiency fold in lipophilicity too, since cheap potency gained simply by making a molecule greasier is often a false economy.