Structure Prediction of Protein Complexes

  • Brian Pierce
  • Zhiping Weng
Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)


Protein-protein interactions are critical for biological function. They directly and indirectly influence the biological systems of which they are a part. Antibodies bind with antigens to detect and stop viruses and other infectious agents. Cell signaling is performed in many cases through the interactions between proteins. Many diseases involve protein-protein interactions on some level, including cancer and prion diseases.


Fast Fourier Transform Root Mean Square Deviation Protein Docking Nuclear Magnetic Resonance Structure Docking Algorithm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abagyan, R., Totrov, M., and Kuznetsov, D. 1994. ICM—A new method for protein modeling and design—Applications to docking and structure prediction from the distorted native conformation. J. Comput. Chem. 15:488–506.CrossRefGoogle Scholar
  2. Aloy, P., Bottcher, B., Ceulemans, H., Leutwein, C., Mellwig, C., Fischer, S., et al. 2004. Structure-based assembly of protein complexes in yeast. Science 303:2026–2029.CrossRefADSGoogle Scholar
  3. Aloy, P., and Russell, R.B. 2002. Interrogating protein interaction networks through structural biology. Proc. Natl. Acad. Sci. USA 99:5896–5901.CrossRefADSGoogle Scholar
  4. Bartel, P.L., and Fields, S. 1995. Analyzing protein-protein interactions using twohybrid system. Methods Enzymol. 254:241–263.CrossRefGoogle Scholar
  5. Betts, M.J., and Sternberg, M.J. 1999. An analysis of conformational changes on protein-protein association: Implications for predictive docking. Protein Eng. 12:271–283.CrossRefGoogle Scholar
  6. Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaminathan, S., and Karplus, M. 1983. CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 4:187–217.CrossRefGoogle Scholar
  7. Canutescu, A.A., Shelenkov, A.A., and Dunbrack, R.L., Jr. 2003. A graph-theory algorithm for rapid protein side-chain prediction. Protein Sci. 12:2001–2014.CrossRefGoogle Scholar
  8. Carugo, O., and Franzot, G. 2004. Prediction of protein-protein interactions based on surface patch comparison. Proteomics 4:1727–1736.CrossRefGoogle Scholar
  9. Chen, R., Li, L., and Weng, Z. 2003a. ZDOCK: An initial-stage protein-docking algorithm. Proteins 52:80–87.CrossRefGoogle Scholar
  10. Chen, R., Mintseris, J., Janin, J., and Weng, Z. 2003b. A protein-protein docking benchmark. Proteins 52:88–91.CrossRefGoogle Scholar
  11. Choe, H., Burtnick, L.D., Mejillano, M., Yin, H. L., Robinson, R.C., and Choe, S. 2002. The calcium activation of gelsolin: Insights from the 3A structure of the G4-G6/actin complex. J. Mol. Biol. 324:691–702.CrossRefGoogle Scholar
  12. Chothia, C., and Janin, J. 1975. Principles of protein-protein recognition. Nature 256:705–708.CrossRefADSGoogle Scholar
  13. Clackson, T., and Wells, J. A. 1995. A hot spot of binding energy in a hormonereceptor interface. Science 267:383–386.CrossRefADSGoogle Scholar
  14. Clore, G. M. 2000. Accurate and rapid docking of protein-protein complexes on the basis of intermolecular nuclear Overhauser enhancement data and dipolar couplings by rigid body minimization. Proc. Nat. Acad. Sci. USA 97:9021–9025.CrossRefADSGoogle Scholar
  15. Clore, G.M., and Schwieters, C.D. 2003. Docking of protein-protein complexes on the basis of highly ambiguous intermolecular distance restraints derived from 1H/15N chemical shift mapping and backbone 15N-1H residual dipolar couplings using conjoined rigid body/torsion angle dynamics. J. Am. Chem. Soci. 125:2902–2912.CrossRefGoogle Scholar
  16. Comeau, S.R., Gatchell, D.W., Vajda, S., and Camacho, C.J. 2004. ClusPro: An automated docking and discrimination method for the prediction of protein complexes. Bioinformatics 20:45–50.CrossRefGoogle Scholar
  17. Connolly, M. L. 1983. Solvent-accessible surfaces of proteins and nucleic acids. Science 221:709–713.CrossRefADSGoogle Scholar
  18. Connolly, M. L. 1986. Shape complementarity at the hemoglobin alpha 1 beta 1 subunit interface. Biopolymers 25:1229–1247.CrossRefGoogle Scholar
  19. Dellis, S., Strickland, K.C., McCrary, W. J., Patel, A., Stocum, E., and Wright, C.F. 2004. Protein interactions among the vaccinia virus late transcription factors. Virology 329:328–336.Google Scholar
  20. Dill, K.A., Phillips, A.T., and Rosen, J. B. 1997. Protein structure and energy landscape dependence on sequence using a continuous energy function. J. Comput. Biol. 4:227–239.CrossRefGoogle Scholar
  21. Dominguez, C., Boelens, R., and Bonvin, A.M. 2003. HADDOCK: A proteinprotein docking approach based on biochemical or biophysical information. J.Am. Chem. Soc. 125:1731–1737.CrossRefGoogle Scholar
  22. Duan, Y., Reddy, B.V, and Kaznessis, Y.N. 2005. Physicochemical and residue conservation calculations to improve the ranking of protein-protein docking solutions. Protein Sci. 14:316–328.CrossRefGoogle Scholar
  23. Dunbrack, R. L., Jr. 2002. Rotamer libraries in the 21st century. Curr. Opin. Struct. Biol. 12:431–440.CrossRefGoogle Scholar
  24. Fischer, D., Lin, S.L., Wolfson, H.L., and Nussinov, R. 1995. A geometry-based suite of molecular docking processes. J. Mol. Biol. 248:459–477.Google Scholar
  25. Fitzjohn, P.W., and Bates, P. A. 2003. Guided docking: First step to locate potential binding sites. Proteins 52:28–32.CrossRefGoogle Scholar
  26. Gabb, H.A., Jackson, R.M., and Sternberg, M.J. 1997. Modelling protein docking using shape complementarity, electrostatics and biochemical information. J. Mol. Biol. 272:106–120.CrossRefGoogle Scholar
  27. Gardiner, E.J., Willett, P., and Artymiuk, P. J. 2001. Protein docking using a genetic algorithm. Proteins 44:44–56.CrossRefGoogle Scholar
  28. Gray, J.J., Moughon, S., Wang, C., Schueler-Furman, O., Kuhlman, B., Rohl, C.A., et al. 2003. Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. J. Mol. Biol. 331:281–299.CrossRefGoogle Scholar
  29. Greer, J., and Bush, B.L. 1978. Macromolecular shape and surface maps by solvent exclusion. Proc. Natl. Acad. Sci. USA 75:303–307.CrossRefADSGoogle Scholar
  30. Halperin, I., Ma, B., Wolfson, H., and Nussinov, R. 2002. Principles of docking: An overview of search algorithms and a guide to scoring functions. Proteins 47:409–443.CrossRefGoogle Scholar
  31. Ho, Y., Gruhler, A., Heilbut, A., Bader, G.D., Moore, L., Adams, S.L., et al. 2002.Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415:180–183.CrossRefADSGoogle Scholar
  32. Honig, B., and Nicholls, A. 1995. Classical electrostatics in biology and chemistry. Science 268:1144–1149.CrossRefADSGoogle Scholar
  33. Inbar, Y., Benyamini, H., Nussinov, R., and Wolfson, H.J. 2005. Combinatorial docking approach for structure prediction of large proteins and multi-molecular assemblies. Phys. Biol. 2:S156–S165.CrossRefADSGoogle Scholar
  34. Janin, J. 1997. The kinetics of protein-protein recognition. Proteins 28:153–161.CrossRefGoogle Scholar
  35. Janin, J. 2005. Assessing predictions of protein-protein interaction: The CAPRI experiment. Protein Sci. 14:278–283.CrossRefGoogle Scholar
  36. Janin, J., Henrick, K., Moult, J., Eyck, L.T., Sternberg, M.J., Vajda, S., et al. 2003. CAPRI: A Critical Assessment of PRedicted Interactions. Proteins 52:2–9.CrossRefGoogle Scholar
  37. Jiang, F., and Kim, S.H. 1991. “Soft docking“: Matching of molecular surface cubes. J. Mol. Biol. 219:79–102.CrossRefGoogle Scholar
  38. Jones, S., and Thornton, J.M. 1996. Principles of protein-protein interactions. Proc. Natl. Acad. Sci. USA 93:13–20.CrossRefADSGoogle Scholar
  39. Katchalski-Katzir, E., Shariv, I., Eisenstein, M., Friesem, A.A., Aflalo, C., and Vakser, I.A. 1992. Molecular surface recognition: Determination of geometric fit between proteins and their ligands by correlation techniques. Proc. Natl. Acad. Sci. USA 89:2195–2199.CrossRefADSGoogle Scholar
  40. Kleanthous, C. 2000. Protein-Protein Recognition. London, Oxford University Press.Google Scholar
  41. Klupp, B.G., Bottcher, S., Granzow, H., Kopp, M., and Mettenleiter, T.C. 2005. Complex formation between the UL16 and UL21 tegument proteins of pseudorabies virus. J. Virol. 79:1510–1522.CrossRefGoogle Scholar
  42. Knegtel, R.M., Kuntz, I.D., and Oshiro, C.M. 1997. Molecular docking to ensembles of protein structures. J. Mol. Biol. 266:424–440.CrossRefGoogle Scholar
  43. Kortemme, T., Morozov, A.V., and Baker, D. 2003. An orientation-dependent hydrogen bonding potential improves prediction of specificity and structure for proteins and protein-protein complexes. J. Mol. Biol. 326:1239–1259.CrossRefGoogle Scholar
  44. Kuntz, I.D., Blaney, J.M., Oatley, S.J., Langridge, R., and Ferrin, T.E. 1982. A geometric approach to macromolecule-ligand interactions. J. Mol. Biol. 161:269–288.CrossRefGoogle Scholar
  45. Lamdan, Y., Schwartz, J.T., and Wolfson, H. J. 1990. Affine invariant model-based object recognition. IEEE Trans. Robotics Autom. 6:578–589.CrossRefGoogle Scholar
  46. Lee, R.H., and Rose, G.D. 1985. Molecular recognition. I. Automatic identification of topographic surface features. Biopolymers 24:1613–1627.CrossRefGoogle Scholar
  47. Lesk, A. M. 2001. Introduction to Protein Architecture: The Structural Biology of Proteins. London, Oxford University Press.Google Scholar
  48. Li, L., Chen, R., and Weng, Z. 2003. RDOCK: Refinement of rigid-body protein docking predictions. Proteins 53:693–707.CrossRefGoogle Scholar
  49. Lu, L., Arakaki, A.K., Lu, H., and Skolnick, J. 2003. Multimeric threadingbased prediction of protein-protein interactions on a genomic scale: Application to the Saccharomyces cerevisiae proteome. Genome Res. 13:1146–1154.CrossRefGoogle Scholar
  50. Mandell, J.G., Roberts, V.A., Pique, M.E., Kotlovyi, V., Mitchell, J.C., Nelson, E., et al. 2001. Protein docking using continuum electrostatics and geometric fit. Protein Eng. 14:105–113.CrossRefGoogle Scholar
  51. Mendez, R., Leplae, R., De Maria, L., and Wodak, S.J. 2003. Assessment of blind predictions of protein-protein interactions: Current status of docking methods. Proteins 52:51–67.CrossRefGoogle Scholar
  52. Meng, E.C., Gschwend, D.A., Blaney, J.M., and Kuntz, I.D. 1993. Orientational sampling and rigid-body minimization in molecular docking. Proteins 17:266–278.CrossRefGoogle Scholar
  53. Mintseris, J., Wiehe, K., Pierce, B., and erson, R., Chen, R., Janin, J., et al. 2005.Protein-Protein Docking Benchmark 2.0: An update. Proteins 60:214–216.CrossRefGoogle Scholar
  54. Mitchell, J.C., Rosen, J.B., Phillips, A.T., and Ten Eyck, L.F. 1999. Coupled optimization in protein docking. Paper presented at the RECOMB.Google Scholar
  55. Miyazawa, S., and Jernigan, R.L. 1996. Residue-residue potentials with a favorable contact pair term and an unfavorable high packing density term, for simulation and threading. J. Mol. Biol. 256:623–644.CrossRefGoogle Scholar
  56. Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., et al. 1998. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 19:1639–1662.CrossRefGoogle Scholar
  57. Mullaney, B.P., and Pallavicini, M.G. 2001. Protein-protein interactions in hematology and phage display. Exp. Hematol. 29:1136–1146.CrossRefGoogle Scholar
  58. Norel, R., Petrey, D., Wolfson, H.J., and Nussinov, R. 1999. Examination of shape complementarity in docking of unbound proteins. Proteins 36:307–317.CrossRefGoogle Scholar
  59. Palma, P.N., Krippahl, L., Wampler, J.E., and Moura, J.J. 2000. BiGGER: A new (soft) docking algorithm for predicting protein interactions. Proteins 39:372–384.CrossRefGoogle Scholar
  60. Phillips, A.T., Rosen, J.B., and Walke, V.H. 1995. Molecular structure determination by convex global underestimation of local energy minima. In P. M. Pardalos, D. Shalloway, and G. Xue (eds.), DIMACS Series in Discrete Mathematics and Theoretical Computer Science (Vol. 23, pp. 181–198). Providence, RI, American Mathematical Society.Google Scholar
  61. Pierce, B., Tong, W., and Weng, Z. 2005. M-ZDOCK: A grid-based approach for Cn symmetric multimer docking. Bioinformatics 21:1472–1478.CrossRefGoogle Scholar
  62. Press, W. H. 2002. Numerical Recipes in C: The Art of Scientific Computing, 2nd ed. London, Cambridge University Press.Google Scholar
  63. Puig, O., Caspary, F., Rigaut, G., Rutz, B., Bouveret, E., Bragado-Nilsson, E., et al. 2001. The tandem affinity purification (TAP) method: A general procedure of protein complex purification. Methods (Duluth) 24:218–229.Google Scholar
  64. Ritchie, D.W., and Kemp, G.J. 2000. Protein docking using spherical polar Fourier correlations. Proteins 39:178–194.CrossRefGoogle Scholar
  65. Sandak, B., Wolfson, H.J., and Nussinov, R. 1998. Flexible docking allowing induced fit in proteins: Insights from an open to closed conformational isomers. Proteins 32:159–174.CrossRefGoogle Scholar
  66. Schneidman-Duhovny, D., Inbar, Y., Nussinov, R., and Wolfson, H.J. 2005. Patch-Dock and SymmDock: Servers for rigid and symmetric docking. Nucleic Acids Res. 33(Web Server issue): W363–W367.CrossRefGoogle Scholar
  67. Shoichet, B.K., and Kuntz, I.D. 1991. Protein docking and complementarity. J. Mol. Biol. 221:327–346.CrossRefGoogle Scholar
  68. Smith, G.R., and Sternberg, M.J. 2002. Prediction of protein-protein interactions by docking methods. Curr. Opin. Struct. Biol. 12:28–35.CrossRefGoogle Scholar
  69. Smith, G.R., Sternberg, M.J., and Bates, P.A. 2005. The relationship between the flexibility of proteins and their conformational states on forming proteinprotein complexes with an application to protein-protein docking. J. Mol. Biol. 347:1077–1101.CrossRefGoogle Scholar
  70. Tovchigrechko, A., Wells, C.A., and Vakser, I.A. 2002. Docking of protein models. Protein. Sci. 11:1888–1896.CrossRefGoogle Scholar
  71. Vajda, S., and Camacho, C.J. 2004. Protein-protein docking: Is the glass half-full or half-empty? Trends Biotechnol. 22(3): 110–116.CrossRefGoogle Scholar
  72. Vakser, I. A. 1995. Protein docking for low-resolution structures. Protein Eng. 8:371–377.CrossRefGoogle Scholar
  73. Wodak, S.J., and Janin, J. 1978. Computer analysis of protein-protein interaction. J. Mol. Biol. 124:323–342.CrossRefGoogle Scholar
  74. Wodak, S. J., and Janin, J. 2002. Structural basis of macromolecular recognition. Adv. Protein Chem. 61:9–73.CrossRefGoogle Scholar
  75. Wodak, S.J., and Mendez, R. 2004. Prediction of protein-protein interactions: The CAPRI experiment, its evaluation and implications. Curr. Opin. Struct. Biol. 14:242–249.CrossRefGoogle Scholar
  76. Zacharias, M. 2003. Protein-protein docking with a reduced protein model accounting for side-chain flexibility. Protein Sci. 12:1271–1282.CrossRefGoogle Scholar
  77. Zacharias, M., and Sklenar, H. 1999. Harmonic modes as variables to approximately account for receptor flexibility in ligand-receptor docking simulations: Application to DNA minor groove ligand complex. J. Comput. Chem. 20:287–300.CrossRefGoogle Scholar
  78. Zhang, C., Liu, S., Zhou, H., and Zhou, Y. 2004. An accurate, residue-level, pair potential of mean force for folding and binding based on the distance-scaled, ideal-gas reference state. Protein Sci. 13:400–411.CrossRefGoogle Scholar
  79. Zhang, C., Vasmatzis, G., Cornette, J.L., and DeLisi, C. 1997. Determination of atomic desolvation energies from the structures of crystallized proteins. J. Mol. Biol. 267:707–726.CrossRefGoogle Scholar
  80. Zhou, H., and Zhou, Y. 2002. Distance-scaled, finite ideal-gas reference state improves structure-derived potentials of mean force for structure selection and stability prediction. Protein Sci. 11:2714–2726.CrossRefGoogle Scholar
  81. Zhu, H., Bilgin, M., Bangham, R., Hall, D., Casamayor, A., Bertone, P., et al. 2001.Global analysis of protein activities using proteome chips. Science 293:2101–2105.CrossRefADSGoogle Scholar
  82. Zielenkiewicz, P., and Rabczenko, A. 1984. Protein-protein recognition: Method for finding complementary surfaces of interacting proteins. J. Theor. Biol. 111:17–30.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Brian Pierce
    • 1
  • Zhiping Weng
    • 1
  1. 1.Department of Biomedical EngineeringBoston UniversityBoston

Personalised recommendations