Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Detailed ab initio prediction of lysozyme–antibody complex with 1.6 Å accuracy


The fundamental event in biological assembly is association of two biological macromolecules. Here we present a successful, accurate ab initio prediction of the binding of uncomplexed lysozyme to the HyHel5 antibody. The prediction combines pseudo Brownian Monte Carlo minimization with a biased–probability global side–chain placement procedure. It was effected in an all–atom representation, with ECEPP/2 potentials complemented with the surface energy, side–chain entropy and electrostatic polarization free energy. The near–native solution found was surprisingly close to the crystallographic structure (root–mean–square deviation of 1.57 Å for all backbone atoms of lysozyme) and had a considerably lower energy (by 20 kcal mol−1) than any other solution.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. Wodak, S.J. & Janin, J. Computer analysis of protein-protein interactions. J. molec. Biol. 124, 323–342 (1978).

    Article  CAS  Google Scholar 

  2. Kuntz, I.D., Blaney, J.M., Oatley, S.J., Langridge, R. & Ferrin, T.E. A geometric approach to macromolecule-ligand interactions. J. molec. Biol. 161, 269–288 (1982).

    Article  CAS  Google Scholar 

  3. Connolly, M.L. Shape complementarity at the hemoglobin α1\β1 Subunit interface. Biopolymers 25, 1229–1247 (1986).

    Article  CAS  Google Scholar 

  4. Warwicker, J. Investigating protein-protein interaction surfaces using a reduced stereochemical and electrostatic model. J. molec. Biol. 206, 381–395 (1989).

    Article  CAS  Google Scholar 

  5. Goodsell, A.S. ; Olson, A.J. Automated docking of substrates to proteins by simulated annealing. Proteins Struct. Funct. Genet. 8, 195–202 (1990).

    Article  CAS  Google Scholar 

  6. Cherfils, J., Duquerroy, S. & Janin, J. Protein-protein recognition analyzed by docking simulation. Proteins 11, 271–280 (1991).

    Article  CAS  Google Scholar 

  7. Jiang, F. & Kim, S.-H. “Soft docking”: matching of molecular surface cubes. J. molec. Biol. 219, 79–102 (1991).

    Article  CAS  Google Scholar 

  8. Shoichet, B.K. & Kuntz, I.D. Protein Docking and Complementarity. J. molec. Biol. 221, 327–346 (1991).

    Article  CAS  Google Scholar 

  9. Shoichet, B.K., Bodian, D.L. & Kuntz, I.D. Molecular docking using shape descriptors. J. comp. Chem. 13, 380–397 (1992).

    Article  CAS  Google Scholar 

  10. Bacon, D.J. & Moult, J. Docking by least-squares fitting of molecular surface patterns. J. molec. Biol. 225, 849–858 (1992).

    Article  CAS  Google Scholar 

  11. Walls, P.H. & Sternberg, M.J.E. New algorithm to model protein-protein recognition based on surface complementarity. J. molec. Biol. 228, 277–297 (1992).

    Article  CAS  Google Scholar 

  12. Pellegrini, M. & Doniah, S. Computer simulation of antibody binding specificity. Proteins 15, 436–444 (1993).

    Article  CAS  Google Scholar 

  13. Sheriff, S. et al. Three-dimensional structure of an antibody-antigen complex. Proc. natn. Acad. Sci. U.S.A. 84, 8075– (1987).

    Article  CAS  Google Scholar 

  14. Padlan, E.A. & Kabat, E.A. Modeling of antibody complex. Meth. Enzym. 203, 3–21 (1991).

    Article  CAS  Google Scholar 

  15. Rini, J.M., Schulze-Gahmen, U., Wilson, I.A. Structural evidence for induced fit as a mechanism for antibody-antigen recognition. Science 255, 959–965 (1992).

    Article  CAS  Google Scholar 

  16. Padlan, E.A., Silverton, E.W., Sheriff, S., Cohen, G.H., Smith-Gill, S.J., Davies, D.R. Structure of an antibody-antigen complex: crystal structure of the HyHEL-10Fab-lysozyme complex. Proc. natn. Acad. Sci. U.S.A. 86, 5938–5942 (1989).

    Article  CAS  Google Scholar 

  17. Fischmann, T.O. et al. Crystallographic refinement of the three-dimensional structure of theFabD1.3-lysozyme complex at 2.5 A resolution. J. biol. Chem. 266, 12915–12920 (1991).

    CAS  PubMed  Google Scholar 

  18. Diamond, R. Refinement of the Structure of Hen Egg-white Lysozyme. J. molec. Biol. 82, 371–391 (1974).

    Article  CAS  Google Scholar 

  19. Abagyan, R.A., Totrov, M.M. & Kuznetsov, D.A. ICM: a new method for structure modelling and design:Applications to docking and structure prediction from the distorted native conformation. J. comp. Chem. (in the press).

  20. Abagyan, R.A. & Totrov, M.M. Biased probability monte carlo conformational searches and electrostatic calculations for peptides and proteins. J. molec. Biol. 235, 983–1002 (1994).

    Article  CAS  Google Scholar 

  21. Totrov, M.M. & Abagyan, R.A. Efficient parallelization of the energy, surface and derivative calculations for internal coordinate mechanics. J. comp. Chem. (in the press).

  22. Bernstein, F.C. et al. The protein data bank: a computer-based archival file for macromolecularstructures. J. molec. Biol. 112, 535–542 (1977).

    Article  CAS  Google Scholar 

  23. Momany, F.A., McGuire, R.F., Burgess, A.W. & Scheraga, H.A. Energy parameters in polypeptides VII. Geometric parameters, partial atomic charges, nonbonded interactions, hydrogen bond interactions, and intrinsic torsional potentials for the naturally occurring amino acids. J. phys. Chem. 79, 2361–2381 (1975).

    Article  CAS  Google Scholar 

  24. Nemethy, G., Pottle, M.S. & Scheraga, H.A. Energy parameters in polypeptides. 9. updating of geometric parameters, nonbonded interactions and hydrogen bond interactions for the naturally occurring amino acids. J. phys. Chem. 87, 1883–1887 (1983).

    Article  CAS  Google Scholar 

  25. Pickersgill, R.W. A rapid method of calculating charge-charge interaction energies in proteins. Protein Eng. 2, 247–248 (1988).

    Article  CAS  Google Scholar 

  26. Abagyan, R.A. & Argos, P. Optimal protocol and trajectory visualization for conformational searches of peptides and proteins. J. molec. Biol. 225, 519–532 (1992).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Cite this article

Totrov, M., Abagyan, R. Detailed ab initio prediction of lysozyme–antibody complex with 1.6 Å accuracy. Nat Struct Mol Biol 1, 259–263 (1994).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing