Binding sites comparisons

It is worth to mention that binding site comparison relies on the entries of the structural protein database. The increasing number of available crystal structures will facilitate the identification of similar binding sites and potential off-targets and is most suitable for large protein families like kinases or proteins with purine containing binding sites (93). 

The second group of approaches, seeking similarities in the shapes and chemical surface properties of binding sites, include recently developed tools such as CavBase [89, 90], eF-Site [91], and SuMo [92]. An earlier technique using surface shape only for binding site comparisons was reported by Rosen et al. [93], The reliability of this geometric surface-matching approach has been shown for the catalytic triad of serine proteases and chorismate mutase. 

Statistics including large and diverse sets of protein structures have revealed that the 20 amino acid residue types exhibit distinctly different levels of flexibility [138], Gin residues appear to be amazingly flexible (given their medium size) and are used in the following section for exemplifying some of the caveats that complicate binding site comparisons. 

Although the problems discussed above can impose some restrictions on the use of binding site comparisons in chemogenomics programs, the broad array of methods available still offers significant support for the majority of cases. Careful assessment of the target structure and the relevant structural data can certainly guide the choice of appropriate methods. For example, the application of methods... 

Clearly, the quantitative methods for describing binding site similarities, required for large-scale database searches in the spirit of omics efforts, still need to be improved. The development of powerful scoring functions is an area of ongoing research, and hopefully some of the shortcomings will be resolved in the near future. Nevertheless, the examples discussed in this section demonstrate, within the realms of possibility, the usefulness of binding site comparison methods. 

Gold, N.D., DeviUe, K., Jackson, R.M. New opportunities for protease ligand-binding site comparisons using SitesBase. Biochem. Soc. Trans. 2007,35, 561-5. 

Batista, ]., Hawkins, P.C., Tolbert, R., and Geballe, M.T. (2014) SiteHoppen a unique tool for binding site comparison. Journal of Cheminformatics, 6 (Suppl. 1), P57. 

Nath D., van der Merwe P. A., Kelm S., Bradfield P. and Crocker P. R. (1995) The amino-terminal immunoglobulin-like domain of sialoadhesin contains the sialic acid binding site. Comparison with CD22, J. Biol. Chem. 270 26184-26191. 

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