Molecular binding

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Molecular binding is an attractive interaction between two molecules that results in a stable association in which the molecules are close to each other. The result of molecular binding is the formation of a molecular complex. A molecular complex in turn is a loose association involving two or more molecules. The attractive bonding between the components of a complex is normally weaker than in a covalent bond.[1]


Molecular binding can be classified into the following types:[2]

  • non-covalent – no chemical bonds are formed between the two interacting molecules hence the association is fully reversible
  • reversible covalent – a chemical bond is formed, however the free energy difference separating the noncovalently-bonded reactants from bonded product is near equilibrium and the activation 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 is thermodynamically much more stable than the reactants such that the reverse reaction does not take place.

Driving force[edit]

In order for the complex to be stable, the free energy of complex by definition must be lower than the solvent separated molecules. The binding may be primarily entropy-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 the hydrophobic effect. Alternatively the binding may be enthalpy-driven where non-covalent attractive forces such as electrostatic attraction, hydrogen bonding, and van der Waals / London dispersion forces are primarily responsible for the formation of a stable complex.[3] 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 as enthalpy-entropy compensation.[4]


The association constant (KI) also known as the binding constant (KA) between the components of complex is the ratio of the concentration of the complex divided by the product of the concentrations of the isolated components at equilibrium:

A+B \rightleftharpoons AB:\log K_{I} =\log \left(\frac{[AB]}{[A][B]} \right)=pK_I


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

Proteins that form stable complexes with other molecules are often referred to as receptors while their binding partners are called ligands.[8]

See also[edit]


  1. ^ "Definition of a molecular complex". Compendium of Chemical Terminology: Gold Book. International Union of Pure and Applied Chemistry. 2012-08-19. 
  2. ^ Smith AJ, Zhang X, Leach AG, Houk KN (January 2009). "Beyond picomolar affinities: quantitative aspects of noncovalent and covalent binding of drugs to proteins". J. Med. Chem. 52 (2): 225–33. doi:10.1021/jm800498e. PMC 2646787. PMID 19053779. 
  3. ^ Miyamoto S, Kollman PA (September 1993). "What determines the strength of noncovalent association of ligands to proteins in aqueous solution?". Proc. Natl. Acad. Sci. U.S.A. 90 (18): 8402–6. doi:10.1073/pnas.90.18.8402. PMC 47364. PMID 8378312. 
  4. ^ Cooper A (October 1999). "Thermodynamic analysis of biomolecular interactions". Curr Opin Chem Biol 3 (5): 557–63. doi:10.1016/S1367-5931(99)00008-3. PMID 10508661. 
  5. ^ Haian Fu (2004). Protein-protein interactions: methods and applications. Totowa, NJ: Humana Press. ISBN 1-58829-120-0. 
  6. ^ Harald Seitz (2007). Analytics of Protein-DNA Interactions (Advances in Biochemical Engineering / Biotechnology). Berlin: Springer. ISBN 3-540-48147-8. 
  7. ^ Gerd Folkers; Hans-Joachim Böhm; Gisbert Schneider; Raimund Mannhold; Hugo Kubinyi (2003). Protein-ligand interactions from molecular recognition to drug design. Weinheim: Wiley-VCH. ISBN 3-527-30521-1. 
  8. ^ Klotz, Irving M. (1997). Ligand-receptor energetics: a guide for the perplexed. Chichester: John Wiley & Sons. ISBN 0-471-17626-5.