Protein Docking in the Absence of Detailed Molecular Structures

  • I. A. Vakser
  • G. V. Nikiforovich


The design of new computational procedures to predict molecular complexes is a fast developing area stimulated by the growing demands of researchers working in various fields of molecular biology and looking for more powerful tools for their investigations. The problem for molecular recognition (docking) approaches may be shortly formulated as following: how to match two molecules with known 3D structures in order to predict the configuration of their complex? In the general case, no additional prior knowledge on binding sites is assumed to be available.


Molecular Recognition Protein Docking Docking Procedure Correct Translation Ligand Orientation 
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.


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  1. 1.
    Kuntz, I.D., Meng, E.C., and Shoichet, B.K., 1994, Structure-based molecular design, Acc. Chem. Res. 27: 117–123.CrossRefGoogle Scholar
  2. 2.
    Kollman, P.A., 1994, Theory of macromolecule-ligand interactions, Curr. Opin. Struct. Biol. 4: 240–245.CrossRefGoogle Scholar
  3. 3.
    Blaney, J.M., and Dixon, J.S., 1993, A good ligand is hard to find: automated docking methods, Perspec. Drug Disc. Des. 1: 301–319.CrossRefGoogle Scholar
  4. 4.
    Cherfils, J., and Janin, J., 1993, Protein docking algorithms: simulating molecular recognition, Curr. Opin. Struct. Biol. 3: 265–269.CrossRefGoogle Scholar
  5. 5.
    Goodford, P.J., 1985, A computational procedure for determining energetically favorable binding sites on biologically important macromolecules, J. Med. Chem. 28: 849–857.PubMedCrossRefGoogle Scholar
  6. 6.
    Warwicker, J., 1989, Investigating protein-protein interaction surfaces using a reduced stereochemical and electrostatic model, J. Mol. Biol. 206: 381–395.PubMedCrossRefGoogle Scholar
  7. 7.
    Goodsell, D.S., and Olson, A.J., 1990, Automated docking of substrates to proteins by simulated annealing, Proteins 8: 195–202.PubMedCrossRefGoogle Scholar
  8. 8.
    Yue, S.-Y., 1990, Distance-constrained molecular docking by simulated annealing, Protein Engng. 4: 177–184.CrossRefGoogle Scholar
  9. 9.
    Caflisch, A., Niederer, P., and Anliker, M., 1992, Monte Carlo docking of oligopeptides to proteins, Pmteins 13: 223–230.CrossRefGoogle Scholar
  10. 10.
    Hart, T.N., and Read, R.J., 1992, A multiple-start Monte Carlo docking method, Proteins 13: 206–222.PubMedCrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    Connolly, M.L., 1986, Shape complementarity at the hemoglobin alphal-betal subunit interface, Biopolymers 25: 1229–1247.PubMedCrossRefGoogle Scholar
  13. 13.
    DesJarlais, R.L., Sheridan, R.P., Seibel, G.L., Dixon, J.S., Kuntz, I.D., and Venkataraghavan, R., 1988, Using shape complementarity as an initial screen in designing ligands for a receptor binding site of known three-dimensional structure, J. Med. Chem. 31: 722–729.PubMedCrossRefGoogle Scholar
  14. 14.
    Jiang, F., and Kim, S.H., 1991, “Soft docking”: matching of molecular surface cubes, J. Mol. Biol. 219: 79–102.Google Scholar
  15. 15.
    Nord, R., Fischer, D., Wolfson, H.J., and Nussinov, R., 1994, Molecular surface recognition by a computer vision-based technique, Protein Engng. 7: 39–46.CrossRefGoogle Scholar
  16. 16.
    Shoichet, B.K., and Kuntz, I.D., 1991, Protein docking and complementarity, J. Mol. Biol. 221: 327–346.PubMedCrossRefGoogle Scholar
  17. 17.
    Katchalski-Katzir, E., Shariv, I., Eisenstein, M., Friesem, A.A., Aflalo, C., and Vakser, I.A., 1992, Molecular surface recognition: determination of of geometric fit between proteins and their ligands by correlation techniques, Proc. Natl. Acad. Sci. U.S.A. 89: 2195–2199.PubMedCrossRefGoogle Scholar
  18. 18.
    Helmer-Citterich, M., and Tramontano, A., 1994, PUZZLE: a new method for automated protein docking based on surface shape complementarity, J. Mol. Biol. 235: 1021–1031.PubMedCrossRefGoogle Scholar
  19. 19.
    Ho, C.M.W., and Marshall, G.R., 1993, SPLICE: a program to assemble partial query solutions from three-dimensional database searches into novel ligands, J. Comput. Aided Mol. Des. 7: 623–647.CrossRefGoogle Scholar
  20. 20.
    Shoichet, B.K., and Kuntz, I.D., 1993, Matching chemistry and shape in molecular docking, Protein Engng. 6: 723–732.CrossRefGoogle Scholar
  21. 21.
    Vakser, I.A., and Aflalo, C., Hydrophobic docking: a proposed enhancement to molecular recognition techniques, Proteins,in press.Google Scholar
  22. 22.
    Wodak, S.J., and Janin, J., 1978, Computer analysis of protein-protein interaction, J. Mol. Biol. 124: 323–342.PubMedCrossRefGoogle Scholar
  23. 23.
    Janin, J., and Chothia, C., 1990, The structure of protein-protein recognition sites, J. Biol. Chem. 265: 16027–16030.PubMedGoogle Scholar
  24. 24.
    Marshall, G.R., 1992, 3D structure of peptide-protein complexes: implications for recognition, Curr. Opin. Struct. Biol. 2: 904–919.Google Scholar
  25. 25.
    Leach, A.R., 1994, Ligand docking to proteins with discrete side-chain flexibility, J. Mol. Biol. 235: 345–356.PubMedCrossRefGoogle Scholar
  26. 26.
    Tello, D., Goldbaum, F.A., Mariuzza, R A, Ysern, X., Schwarz, F.P., and Poljak, R.J., 1993, Tree-dimensional structure and thermodynamics of antigen binding by anti-lysozyme antibodies, Biochem. Soc. Trans. 21: 943–946.PubMedGoogle Scholar
  27. 27.
    Lawrence, M.C., and Colman, P.M., 1993, Shape complementarity at protein/protein interfaces, J. Mol. Biol. 234: 946–950.PubMedCrossRefGoogle Scholar
  28. 28.
    Vakser, I.A., 1995, Protein docking for low-resolution structures, Protein Engng. 8: 371–377.CrossRefGoogle Scholar
  29. 29.
    Abola, E.E., Bernsein, F.C., Bryant, S.H., Koetzle, T.L., and Weng, J., 1987, Protein Databank, in: Crystallographic Databases–Information Content, Software Systems, Scientific Applications. Allen, F.H., Bergerhoff, G., and Sievers, R. eds., Data Commission of the International Union of Crystallography, Bonn, pp 107–132.Google Scholar
  30. 30.
    Fermi, G., Perutz, M.F., Shaanan, B., and Fourme, R., 1984, The crystal structure of human deoxyhaemoglobin at 1.74 A resolution, J. Mol. Biol. 175: 159–174.PubMedCrossRefGoogle Scholar
  31. 31.
    Ladner, R.C., Heidner, E.G., and Perutz, M.F., 1977, The structure of horse methaemoglobin at 2.0 angstroms resolution, J. Mol. Biol. 114: 385–414.PubMedCrossRefGoogle Scholar
  32. 32.
    Marquart, M., Walter, J., Deisenhofer, J., Bode, W., and Huber, R., 1983, The geometry of the reactive site and of the peptide groups in trypsin, trypsinogen and its complexes with inhibitors, Acta Crystallog., Sect. B 39: 480–490.CrossRefGoogle Scholar
  33. 33.
    Fujinaga, M., Sielecki, A.R., Read, R.J., Ardelt, W., Laskowski, M. Jr, and James, M.N.G., 1987, Crystal and molecular structures of the complex of aplpha-chymotrypsin with its inhibitor turkey ovomucoid third domain at 1.8 angstroms resolution, J. Mol. Biol. 195: 397–418.PubMedCrossRefGoogle Scholar
  34. 34.
    McPhalen, C.A., and James, M.N.G., 1988, Structural comparison of two serine proteinase-protein inhibitor complexes: eglin-c-subtilisin Carlsberg and CI-2-subtilisin Novo, Biochemistry 27: 6582–6598.PubMedCrossRefGoogle Scholar
  35. 35.
    Suguna, K., Bott, R.R., Padlan, E.A., Subramanian, E., Sheriff, S., Cohen, G.H., and Davies, D.R., 1987, Structure and refinement at 1.8 A resolution of the aspartic proteinase from Rhizopus chinensis, J. Mol. Biol. 196: 877–900.PubMedCrossRefGoogle Scholar
  36. 36.
    Brick, P., Bhat, T.N., and Blow, D.M., 1989, Structure of tyrosyl-tRNA synthetase refined at 2.3 angstroms resolution. Interaction of the enzyme with the tyrosyl adenylate intermediate, J. Mol. Biol. 208: 83–98.PubMedCrossRefGoogle Scholar
  37. 37.
    Madden, D.R., Gorga, J.C., Strominger, J.L., and Wiley, D.C., 1992, The three-dimensional structure of HLA-B27 at 2.1 angstroms resolution suggests a general mechanism for tight peptide binding to MHC, Cell 70: 1035–1048.PubMedCrossRefGoogle Scholar
  38. 38.
    Sheriff, S., Silverton, E.W., Padlan, E.A., Cohen, G.H., Smith-Gill, S.J., Finzel, B.C., and Davies, D.R., 1987, Three-dimensional structure of an antibody-antigen complex, Proc. Natl. Acad. Sci. U.S.A. 84: 8075–8079.PubMedCrossRefGoogle Scholar
  39. 39.
    Rini, J.M., Stanfield, R.L., Stura, E.A., Salinas, P.A., Profy, A.T., and Wilson, I.A., 1993, Crystal structure of an HIV-1 neutralizing antibody 50.1 in complex with its V3 loop peptide antigen, Proc. Natl. Acad. Sci. U.S.A. 90: 6325–6329.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • I. A. Vakser
    • 1
  • G. V. Nikiforovich
    • 1
  1. 1.Center for Molecular DesignWashington UniversitySt. LouisUSA

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