Abstract
Vicinity analysis (VA) is a new methodology developed to identify similarities between protein binding sites based on their three-dimensional structure and the chemical similarity of matching residues. The major objective is to enable searching of the Protein Data Bank (PDB) for similar sub-pockets, especially in proteins from different structural and biochemical series. Inspection of the ligands bound in these pockets should allow ligand functionality to be identified, thus suggesting novel monomers for use in library synthesis. VA has been developed initially using the ATP binding site in kinases, an important class of protein targets involved in cell signalling and growth regulation. This paper defines the VA procedure and describes matches to the phosphate binding sub-pocket of cyclin-dependent protein kinase 2 that were found by searching a small test database that has also been used to parameterise the methodology.
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Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissag H, Shindyalov IN, Bourne P (2000) Nucleic Acids Res 125:235–242. doi:10.1093/nar/28.1.235
Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Nucleic Acids Res 25:3389–3402. doi:10.1093/nar/25.17.3389
Orengo CA, Michie AD, Jones S, Jones DT, Swindells MB, Thornton JM (1997) Structure 5:1093–1108. doi:10.1016/S0969-2126(97)00260-8
Schmitt S, Kuhn D, Klebe G (2002) J Mol Biol 323:387–406. doi:10.1016/S0022-2836(02)00811-2
Guoguang L (2000) J Appl Cryst 1:176–183
Sacan A, Oztuck O, Feratosmanoglu H, Wang Y (2007) Bioinformatics 23:709–716. doi:10.1093/bioinformatics/btl685
Wei L, Altman RB (1998) Pac Symp Biocomput 3:497–508
Hendlich M, Bergner A, Gunther J, Klebe G (2003) J Mol Biol 326:607–620. doi:10.1016/S0022-2836(02)01408-0
Spriggs VR, Artymiuk PJ, Willett P (2003) J Chem Inf Comput Sci 43:412–421. doi:10.1021/ci0255984
Ullman J (1976) J ACM 23:31–42. doi:10.1145/321921.321925
Kleywegt GJ (1999) J Mol Biol 285:1887–1897. doi:10.1006/jmbi.1998.2393
Samudrala R, Moult J (1998) J Mol Biol 279:287–302. doi:10.1006/jmbi.1998.1689
Hofbauer C, Lohninger H, Aszódi A (2004) J Chem Inf Comput Sci 44:837–847. doi:10.1021/ci0342371
Brooks BR, Bruccoleri RE, Olafson DJ, States DJ, Swaminathan S, Karplus M (1983) J Comput Chem 4:187–217. doi:10.1002/jcc.540040211
Sobolev V, Sorokine A, Prilusky J, Abola EE, Edelman M (1999) Bioinformatics 15:327–332. doi:10.1093/bioinformatics/15.4.327
Helberg S, Sjostrom M, Skagerberg B, Wold S (1987) J Med Chem 30:1126–1135. doi:10.1021/jm00390a003
Gardiner EJ, Willet P (2000) J Chem Inf Comput Sci 40:273–279. doi:10.1021/ci990262o
Harary F (1994) Graph theory. Addison-Wesley, Reading, MA
Bron C, Kerbosch J (1973) Commun ACM 16:575–577. doi:10.1145/362342.362367
SYBYL, Tripos Associates, St Louis, MO
Holm L, Park J (2000) Bioinformatics 16:566–567. doi:10.1093/bioinformatics/16.6.566
Acknowledgements
We would like to thank Drs V.S. Rose and C.J. Harris for helpful comments and support for this work. A.M.G. acknowledges financial support from Biofocus DPI.
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McGready, A., Stevens, A., Lipkin, M. et al. Vicinity analysis: a methodology for the identification of similar protein active sites. J Mol Model 15, 489–498 (2009). https://doi.org/10.1007/s00894-008-0424-7
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DOI: https://doi.org/10.1007/s00894-008-0424-7