demibinding

Demibinding is a mode of molecular interaction in which a multivalent ligand binds a target at only one of its sites, producing partial engagement. The term reflects the demi prefix meaning half and is used in multivalency and avidity discussions. It is distinct from monovalent binding, where a single site binds, and from full bivalent binding, where both sites engage.

Mechanisms underlying demibinding include asymmetry between binding partners, steric hindrance, and conformational changes after the first binding event that reduce accessibility or affinity at the second site. Allosteric effects and spacing constraints between receptors can further favor demibinding. In some cases, demibinding is a kinetically stable intermediate that may progress to full binding under different conditions.

Thermodynamically, demibinding can be described by sequential binding steps with two constants. If the second-site constant is much smaller than the first, occupancy concentrates on the first-bound state, yielding intermediate avidity that influences crosslinking and overall binding strength. Demibinding thus contributes to nuanced binding behavior in crowded or densely functionalized environments.

Measurement and examples include methods such as surface plasmon resonance, isothermal titration calorimetry, and single-molecule fluorescence to detect partial occupancy and distinguish mono- from bivalent states. Examples cited in the literature include antibodies with suboptimal epitope spacing and engineered ligands in which only one binding module engages a receptor.

Applications and terminology: Demibinding is relevant to drug design, sensors, and materials science where tuning binding strength and specificity is important. The term is not universally used; some literature describes similar states as partial binding or mono-valent binding.