Volume 8 Supplement 8
Variation of geometrical and physicochemical properties in protein binding pockets and their ligands
© Kahraman et al; licensee BioMed Central Ltd. 2007
Published: 20 November 2007
Physicochemical complementarity is commonly believed to be the driving force for molecular binding. The complementarity for example of electrostatic potentials is regarded as the force that draws the ligand from the solvent into the binding site . If this hypothesis is true, the same ligand should encounter complementarity environmental properties in all proteins to which it binds. We have used our recently published ligand and binding pocket matching algorithm  to test this common assumption by searching for property distributions that are similar for the same ligand bound to different proteins.
The algorithm bases on real spherical harmonic functions, which are applicable to approximate any property function on a unit sphere. These property functions can either be of geometrical or physicochemical nature. For our current analysis we used the shape of binding pockets to test their geometrical similarity and mapped electrostatic, van der Waals and hydrophobicity potentials of the protein on the ligand surface to simulate the physicochemical forces that a ligand may feel in its binding site.
These results demonstrate that binding sites that bind the same ligand can exhibit a large variation of properties by facing different physicochemical forces within different binding sites. The results urge a re-evaluation of the total contribution of some physicochemical properties to molecular recognition and the factors that drive molecular binding.
The molecules in the figure were rendered using PyMOL (W.L. DeLano, http://pymol.sourceforge.net/).
- Livesay DR, Jambeck P, Rojnuckarin A, Subramaniam S: Conservation of electrostatic properties within enzyme families and superfamilies. Biochemistry 2003, 42(12):3464–3473. 10.1021/bi026918fView ArticlePubMedGoogle Scholar
- Kahraman A, Morris RJ, Laskowski RA, Thornton JM: Shape variation in protein binding pockets and their ligands. J Mol Biol 2007, 368: 283–301. 10.1016/j.jmb.2007.01.086View ArticlePubMedGoogle Scholar
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res 2000, 28: 235–242. 10.1093/nar/28.1.235PubMed CentralView ArticlePubMedGoogle Scholar
- Conti E, Stachelhaus T, Marahiel MA, Brick P: Structural basis for the activation of phenylalanine in the non-ribosomal biosynthesis of gramicidin S. Embo J 1997, 16: 4174–4183. 10.1093/emboj/16.14.4174PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd.