Comparative Analysis of Techniques Oriented on the Recognition of Ligand Binding Area in Proteins

Part of the Focus on Structural Biology book series (FOSB, volume 8)


This chapter presents an analysis of the various models implemented by software packages which enable computerized identification of ligand binding sites.


Geometric analysis Knowledge mining F-measure MCC ROC curve Precision Recall True positive False positive True negative False negative Sensitivity Comparative analysis Receiver operating characteristic False positive rate True positive rate CASTp Pocket-finder QSite-finder SuMo ConSurf Computed atlas of surface topography of proteins Conservative residues SuMo – surfing the molecules Target protein Easy proteins Hard proteins Fuzzy oil drop 


  1. Altman DG, Bland JM (1994) Diagnostic tests 1: sensitivity and specificity. BMJ 308(6943):1552PubMedCrossRefGoogle Scholar
  2. Altschul S, Madden T, Schaffer A, Zhang J, Zhang Z, Miller W, Lipman D (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402PubMedCrossRefGoogle Scholar
  3. Ashkenazy H, Erez E, Martz E, Pupko T, Ben-Tal N (2010) ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucleic Acids Res. doi: 10.1093/nar/gkq399, PMID: 20478830
  4. Baldi P, Brunak S, Chauvin Y, Andersen CAF, Nielsen H (2000) Assessing the accuracy of prediction algorithms for classification: an overview. Bioinformatics 16:412–424PubMedCrossRefGoogle Scholar
  5. Banach M, Prymula K, Jurkowski W, Konieczny L, Roterman I (2012) Fuzzy oil drop model to interpret the structure of antifreeze proteins and their mutants. J Mol Model 18(1):229–237Google Scholar
  6. Binkowski TA, Naghibzadeh S, Liang J (2003) CASTp: computed atlas of surface topography of proteins. Nucleic Acids Res 31:3352–3355PubMedCrossRefGoogle Scholar
  7. Carugo O (2007) Detailed estimation of bioinformatics prediction reliability through the fragmented prediction performance plots. BMC Bioinformatics 8:380, PMID:17931407PubMedCrossRefGoogle Scholar
  8. Chenna R, Sugawara H, Koike T, Lopez R, Gibson TJ, Higgins DG, Thompson JD (2003) Multiple sequence alignment with the clustal series of programs. Nucleic Acids Res 31(13):3497–3500PubMedCrossRefGoogle Scholar
  9. Dundas J, Ouyang Z, Tseng J, Binkowski A, Turpaz Y, Liang J (2006) CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues. Nucleic Acids Res 34:W116–W118PubMedCrossRefGoogle Scholar
  10. Edelsbrunner H (1995) The union of balls and its dual shape. Disc Comput Geom 13:415–440CrossRefGoogle Scholar
  11. Edelsbrunner H, Mucke EP (1994) Three-dimensional alpha shapes. ACM Trans Graphics 13:43–72CrossRefGoogle Scholar
  12. Edelsbrunner H, Shah NR (1996) Incremental topological flipping works for regular triangulations. Algorithmica 15:223–241CrossRefGoogle Scholar
  13. Edelsbrunner H, Facello M, Fu P, Liang J (1995) Measuring proteins and voids in proteins. In: Proceedings of the 28th annual Hawaii international conference on system sciences. IEEE Computer Society Press, Los Alamitos, pp 256–264Google Scholar
  14. Edelsbrunner H, Facello M, Liang J (1998) On the definition and the construction of pockets in macromolecules. Disc Appl Math 88:83–102CrossRefGoogle Scholar
  15. Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32(5):1792–1797CrossRefGoogle Scholar
  16. Facello MA (1995) Implementation of a randomized algorithm for Delaunay and regular triangulations in three dimensions. Comput Aided Geom Des 12:349–370CrossRefGoogle Scholar
  17. Fawcett T (2006) An introduction to ROC analysis. Pattern Recognit Lett 27:861–874CrossRefGoogle Scholar
  18. Goldenberg O, Erez E, Nimrod G, Ben-Tal N (2009) The ConSurf-DB: pre-calculated evolutionary conservation profiles of protein structures. Nucleic Acids Res 37, Database issue D323–D327Google Scholar
  19. Hendlich M, Rippmann F, Barnickel G (1997) LIGSITE: automatic and efficient detection of potential small molecule-binding sites in proteins. J Mol Graph Model 15:359–363PubMedCrossRefGoogle Scholar
  20. Jambon M, Imberty A, Deléage G, Geourjon G (2003) A new bioinformatics approach to detect common 3D sites in protein structures. Proteins 52:137–145PubMedCrossRefGoogle Scholar
  21. Jambon M, Andrieu O, Combet C, Deléage G, Delfaud F, Geourjon C (2005) The SuMo server: 3D search for protein functional sites. Bioinformatics 21:3929–3930PubMedCrossRefGoogle Scholar
  22. Joosten V, van Berkel WJ (2007) Flavoenzymes. Curr Opin Chem Biol 11(2):195–202PubMedCrossRefGoogle Scholar
  23. Kamburov A, Pentchev K, Galicka H, Wierling C, Lehrach H, Herwig R (2011) ConsensusPathDB: toward a more complete picture of cell biology. Nucleic Acid res, 39 (Database issue):D712–D717Google Scholar
  24. Konieczny L, Brylinski M, Roterman I (2006) Gauss-function-based model of hydrophobicity density in proteins. In Silico Biol 6:15–22PubMedGoogle Scholar
  25. Landau M, Mayrose I, Rosenberg Y, Glaser F, Martz E, Pupko T, Ben-Tal N (2005) ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res 33:W299–W302PubMedCrossRefGoogle Scholar
  26. Laskowski RA (2009) PDBsum new things. Nucleic Acids Res 37:D355–D359PubMedCrossRefGoogle Scholar
  27. Laurie ATR, Jackson RM (2005) Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites. Bioinformatics 21:1908–1916PubMedCrossRefGoogle Scholar
  28. Liang J, Edelsbrunner H, Woodward C (1998a) Anatomy of protein pockets and cavities: measurement of binding site geometry and implications for ligand design. Protein Sci 7:1884–1897PubMedCrossRefGoogle Scholar
  29. Liang J, Edelsbrunner H, Fu P, Sudhakar PV, Subramaniam S (1998b) Analytical shape computation of macromolecules. II. Identification and computation of inaccessible cavities in proteins. Proteins Struct Funct Genet 33:18–29PubMedCrossRefGoogle Scholar
  30. Matthews BW (1975) Comparison of the predicted and observed secondary structure of T4 phage lysozyme. Biochim Biophys Acta 405:442–451PubMedCrossRefGoogle Scholar
  31. Mayrose I, Graur D, Ben-Tal N, Pupko T (2004) Comparison of site-specific rate-inference methods for protein sequences: empirical Bayesian methods are superior. Mol Biol Evol 21:1781–1791PubMedCrossRefGoogle Scholar
  32. Olson DL, Delen D (2008) Advanced data mining techniques. Springer-Verlag Berlin, Heidelberg, p 138. ISBN 3540769161Google Scholar
  33. Pollak N, Dölle C, Ziegler M (2007) The power to reduce: pyridine nucleotides – small molecules with a multitude of functions. Biochem J 402:205–218PubMedCrossRefGoogle Scholar
  34. Prymula K, Jadczyk T, Roterman I (2011) Catalytic residues in hydrolases: analysis of methods designed for ligand-binding site prediction. J Comput Aided Mol Des 25(2):117–133PubMedCrossRefGoogle Scholar
  35. Pupko T, Bell RE, Mayrose I, Glaser F, Ben-Tal N (2002) Rate4Site: an algorithmic tool for the identification of functional regions in proteins by surface mapping of evolutionary determinants within their homologues. Bioinformatics 18:71–77CrossRefGoogle Scholar
  36. Rose PW, Beran B, Bi C, Bluhm WF, Dimitropoulos D, Goodsell DS, Prlic A, Quesada M, Quinn GB, Westbrook JD, Young J, Yukich B, Zardecki C, Berman HM, Bourne PE (2011) The RCSB Protein Data Bank: redesigned web site and web services. Nucleic Acids Res. 39 (Database issue):D392–D401Google Scholar
  37. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680PubMedCrossRefGoogle Scholar
  38. Tsai C-J, Ma B, Nussinov R (2009) Protein-protein interaction networks: how can a hub protein bind so many different partners? Trends Biochem Sci 34(12):594–600PubMedCrossRefGoogle Scholar
  39. van Rijsbergen CV (1979) Information retrieval, 2nd edn. Butterworth, London; Boston. ISBN 0-408-70929-4Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Faculty of Physics, Astronomy and Applied Computer ScienceJagiellonian UniversityCracowPoland
  2. 2.Department of Bioinformatics and TelemedicineJagiellonian University – Medical CollegeCracowPoland
  3. 3.Computational Biology Group, Luxembourg Centre for Systems BiomedicineUniversity of LuxembourgEsch-BelvalLuxembourg

Personalised recommendations