Protein–Ligand Interactions: Energetic Contributions and Shape Complementarity


Protein–ligand interactions include two components: energetic contributions and shape complementarity.

Keywords: hydrophobic effect; hydrogen bonds; shape complementarity; molecular recognition; receptor–ligand interactions

Figure 1.

Examples of protein–protein interfaces. (a) Cytochrome C′ (PDB code 1bbhAB) displays a strong hydrophobic effect. The two chains are displayed in different colours and the backbones of the amino acids belonging to the interface are shown in darker colours. Only the side‐chain of the residues which are actually in contact across the interface as well as on the surface are drawn. The hydrophobic residues are yellow and hydrophilic residues are in cyan.

Figure 2.

Barnase barstar complex (PDB code 1bgsBF) displays a weak hydrophobic effect. The colour scheme is the same as in Figure .



Cherfils J and Janin J (1993) Protein docking algorithms: simulating molecular recognition. Current Opinion in Structural Biology 3: 265–269.

Connolly M (1983) Solvent‐accessible surfaces of proteins and nucleic acids. Science 221: 709–713.

Dunbrack R, Gerloff D, Bower M, Chen X, Lichtarge O and Cohen F (1997) Meeting review: the second meeting on the critical assessment of techniques for protein structure prediction (casp2). Folding & Design 1: R27–R42.

Fischer D, Lin SL, Wolfson H and Nussinov R (1995) A geometry‐based suite of molecular docking processes. Journal of Molecular Biology 248: 459–477.

Gabb HA, Jackson RM and Sternberg MJE (1997) Modelling protein docking using shape complementarity, electrostatics and biochemical information. Journal of Molecular Biology 272: 106–120.

Jackson R, Gabb H and Sternberg M (1998) Rapid refinement of protein interfaces incorporating solvation: application to the docking problem. Journal of Molecular Biology 276: 265–285

Jones G, Willet P, Glen R, Leach A and Taylor R (1997) Development and validation of a genetic algorithm for flexible docking. Journal of Molecular Biology 267: 727–748.

Katchalski‐Katzir E, Shariv L, Eisenstein M, Friesem A, Aflalo C and Vakser I (1992) Molecular surface recognition: determination of geometric fit between protein and their ligands by correlation techniques. Proceedings of the National Academy of Sciences of the USA 89: 2195–2199.

Kuntz I, Blaney J, Oatley S, Langridge R and Ferrin T (1982) A geometric approach to macromolecule–ligand interactions. Journal of Molecular Biology 161: 269–288.

Ladbury JE (1996) Just add water! The effect of water on the specificity of protein–ligand binding sites and its potential application to drug design. Chemistry and Biology 3: 973–980.

Lengauer T and Rarey M (1996) Computational methods for biomolecular docking. Current Opinion in Structural Biology 6: 402–406.

Norel R, Lin SL, Wolfson H and Nussinov R (1995) Molecular surface complementarity at protein–protein interfaces: the critical role played by surface normals at well placed, sparse points in docking. Journal of Molecular Biology 252: 263–273.

Rarey M, Wefing S and Lengauer T (1996) Placement of medium‐sized molecular fragments into active sites of proteins. Journal of Computer‐Aided Molecular Design 10: 41–54.

Robertson AD and Murphy KP (1997) Protein structure and the energetics of protein stability. Chemistry Reviews 97: 1251–1267.

Sandak B, Wolfson H and Nussinov R (1998) Flexible docking allowing induced fit in proteins: Insights from an open to closed conformational isomers. Proteins. 32: 159–174.

Stites WE (1997) Protein–protein interactions: Interface structure, binding thermodynamics, and mutational analysis. Chemistry Reviews 97: 1233–1250.

Tsai C‐J, Lin SL, Wolfson H and Nussinov R (1996) A dataset of protein–protein interfaces generated with a sequence‐order‐independent comparison technique. Journal of Molecular Biology 260: 604–620.

Tsai C‐J, Lin SL, Wolfson H and Nussinov R (1997) Studies of protein–protein interfaces: Statistical analysis of the hydrophobic effect. Protein Science 6: 51–62.

Xu D, Tsai C‐J and Nussinov R (1997a) Hydrogen bonds and salt bridges across protein–protein interfaces. Protein Engineering 10: 999–1012.

Xu D, Lin S and Nussinov R (1997b) Protein binding versus protein folding: The role of hydrophilic bridges in protein associations. Journal of Molecular Biology 265: 68–84.

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Tsai, Chung‐Jung, Norel, Raquel, Wolfson, Haim J, Maizel, Jacob V, and Nussinov, Ruth(Apr 2001) Protein–Ligand Interactions: Energetic Contributions and Shape Complementarity. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0001343]