Identification of Protein–Protein Interactions


Protein–protein interactions are the mechanisms underlying many important biological processes. Prediction of protein–protein interactions is performed using a variety of computational methods that employ both ‘first principles’ biophysical calculations as well as knowledge‐based informatics techniques.

Keywords: protein interactions; molecular docking; molecular recognition; binding energy; noncovalent bonds

Figure 1.

The Lennard–Jones potential models the van der Waals interaction and steric repulsion between a pair of atoms. The precise shape of the curve is dependent upon the atom types. In each case, however, the characteristic shape has a favourable ‘well’ near the position of the global minimum, a steep barrier to atomic collision, and a ‘tail’ that quickly tends toward zero.

Figure 2.

The thermodynamic cycle is a convenient way to calculate the desolvation penalty for binding two proteins in solution. The change in free energy for binding in solution is equal to the change in free energy for binding in vacuum plus the difference between the free energy for solvating the molecules as a complex and individually.

Figure 3.

A ‘united atom’ model combines heavy atoms, such as carbon and nitrogens, with their bound hydrogens in order to create meta‐atoms that reflect the size and biochemical properties of the group. In the figure, a benzene molecule has been recast as two CH3 groups and two CH2 groups. This provides computational efficiency when doing energy calculations, since the 14‐atom benzene molecule has been replaced with four united atoms. Polar hydrogens should not be modelled using united atoms, since atomic level detail of hydrogen bonds is desirable.



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Gilson ME (2002) Introduction to continuum electrostatics, with molecular applications.

Janin J, Henrick K, Moult J et al. (2003) CAPRI: A critical assessment of predicted interactions. Proteins Structure Function and Genetics 52 (1): 2–9.

Jones S and Thornton JM (1996) Principles of protein–protein interactions. Proceedings of the National Academy of Sciences of the USA 93: 13–20.

Further Reading

Bourne PE and Weissig H (eds) (2003) Structural Bioinformatics. Wiley‐Liss.

Branden CI and Tooze J (1999) Introduction to Protein Structure, 2nd edn. Garland Publishing.

Leach AM (2001) Molecular Modeling: Principles and Applications, 2nd edn. Englewood Cliffs, NJ: Prentice‐Hall.

Lesk AM (2001) Introduction to Protein Architecture: The Structural Biology of Proteins. Oxford: Oxford University Press.

Schlick T (2002) Molecular Modeling and Simulation. Berlin: Springer.

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Mitchell, Julie C(Jan 2006) Identification of Protein–Protein Interactions. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0004107]