overbind

Overbind is the phenomenon where interactions between molecules bind more extensively than intended, leading to reduced specificity, receptor saturation, or off-target effects. It most commonly arises when concentrations of a binding partner exceed the capacity of available binding sites, or when surfaces present in an assay attract non-target molecules due to hydrophobic or charged interactions. The term is used across disciplines, including biochemistry, pharmacology, and analytical science, to describe the transition from specific to non-specific binding as binding forces are overcome by mass action.

In biochemistry and pharmacology, overbind can cause a ligand to occupy not only its primary target but also secondary or low-affinity sites, resulting in undesirable pharmacodynamic or pharmacokinetic effects. In diagnostic assays, excessive probe or antibody concentrations can raise background signals and obscure true positives. On surfaces used for immobilized binding, high ligand density can promote clustering and non-specific adhesion, compounding interpretation errors.

Mitigation strategies include optimizing concentrations to balance sensitivity and specificity, using blocking reagents or passivation to reduce non-specific interactions, employing controls and competitive binding assays to quantify specific binding, and selecting ligands with higher affinity and selectivity. Kinetic analyses and proper model fitting can help distinguish specific from non-specific binding, and cross-reactivity testing can identify off-target binding patterns.

See also: binding affinity, saturation, non-specific binding, receptor pharmacology.