Molecular binding is an attractive interaction between twomolecules that results in a stable association in which the molecules are in close proximity to each other. It is formed when atoms or molecules bind together by sharing of electrons. It often, but not always, involves somechemical bonding.

In some cases, the associations can be quite strong—for example, the proteinstreptavidin and the vitaminbiotin have adissociation constant (reflecting the ratio between bound and free biotin) on the order of 10⁻¹⁴—and so the reactions are effectively irreversible. The result of molecular binding is sometimes the formation of a molecular complex in which the attractive forces holding the components together are generallynon-covalent, and thus are normally energetically weaker thancovalent bonds.

Molecular binding occurs in biological complexes (e.g., between pairs or sets of proteins, or between a protein and a small moleculeligand it binds) and also in abiologic chemical systems, e.g. as in cases ofcoordination polymers andcoordination networks such asmetal-organic frameworks.

Molecular binding can be classified into the following types:^[1]

• Non-covalent – no chemical bonds are formed between the two interacting molecules hence the association is fully reversible
• Reversiblecovalent – a chemical bond is formed, however thefree energy difference separating the noncovalently-bonded reactants from bonded product is nearequilibrium and theactivation barrier is relatively low such that the reverse reaction which cleaves the chemical bond easily occurs
• Irreversible covalent – a chemical bond is formed in which the product isthermodynamically much more stable than the reactants such that the reverse reaction does not take place.

Bound molecules are sometimes called a "molecular complex"—the term generally refers tonon-covalent associations.^[2] Non-covalent interactions can effectively become irreversible; for example,tight binding inhibitors ofenzymes can have kinetics that closely resemble irreversible covalent inhibitors. Among the tightest known protein–protein complexes is that between the enzymeangiogenin andribonuclease inhibitor; the dissociation constant for the human proteins is 5x10⁻¹⁶ mol/L.^[3][4] Another biological example is the binding proteinstreptavidin, which has extraordinarily high affinity forbiotin (vitamin B7/H,dissociation constant, K_d ≈10⁻¹⁴ mol/L).^[5] In such cases, if the reaction conditions change (e.g., the protein moves into an environment where biotin concentrations are very low, or pH or ionic conditions are altered), the reverse reaction can be promoted. For example, the biotin-streptavidin interaction can be broken by incubating the complex in water at 70 °C, without damaging either molecule.^[6] An example of change in local concentration causing dissociation can be found in theBohr effect, which describes the dissociation of ligands fromhemoglobin in the lung versus peripheral tissues.^[5]

Some protein–protein interactions result incovalent bonding,^[7] and somepharmaceuticals areirreversible antagonists that may or may not be covalently bound.^[8]Drug discovery has been through periods when drug candidates that bind covalently to their targets are attractive and then are avoided; the success ofbortezomib madeboron-based covalently binding candidates more attractive in the late 2000s.^[9][10]

In order for the complex to be stable, thefree energy of complex by definition must be lower than the solvent separated molecules. The binding may be primarilyentropy-driven (release of ordered solvent molecules around the isolated molecule that results in a net increase of entropy of the system). When the solvent is water, this is known as thehydrophobic effect. Alternatively, the binding may beenthalpy-driven where non-covalent attractive forces such aselectrostatic attraction,hydrogen bonding, andvan der Waals /London dispersion forces are primarily responsible for the formation of a stable complex.^[11] Complexes that have a strong entropy contribution to formation tend to have weak enthalpy contributions. Conversely complexes that have strong enthalpy component tend to have a weak entropy component. This phenomenon is known asenthalpy-entropy compensation.^[12]

The strength of binding between the components of molecular complex is measured quantitatively by thebinding constant (K_A), defined as the ratio of the concentration of the complex divided by the product of the concentrations of the isolated components at equilibrium in molar units:

${\displaystyle A+B\rightleftharpoons AB:\log K_A=\log \left(\frac{[AB]}{[A][B]}\right)=-p{K}_A}$

When the molecular complex prevents the normal functioning of anenzyme, thebinding constant is also referred to asinhibition constant (K_I).

Molecules that can participate in molecular binding includeproteins,nucleic acids,carbohydrates,lipids, and small organic molecules such asdrugs. Hence the types of complexes that form as a result of molecular binding include:

• protein–protein^[13]
• protein–DNA^[14]
• protein–hormone
• protein–drug^[15]

Proteins that form stable complexes with other molecules are often referred to asreceptors while their binding partners are calledligands.^[16]

• Receptor (biochemistry)
• Supramolecular chemistry

• Medicinal chemistry
• Molecular physics

• Articles with short description
• Short description matches Wikidata