Modelling protein docking using shape complementarity, electrostatics and biochemical information

J Mol Biol. 1997 Sep 12;272(1):106-20. doi: 10.1006/jmbi.1997.1203.


A protein docking study was performed for two classes of biomolecular complexes: six enzyme/inhibitor and four antibody/antigen. Biomolecular complexes for which crystal structures of both the complexed and uncomplexed proteins are available were used for eight of the ten test systems. Our docking experiments consist of a global search of translational and rotational space followed by refinement of the best predictions. Potential complexes are scored on the basis of shape complementarity and favourable electrostatic interactions using Fourier correlation theory. Since proteins undergo conformational changes upon binding, the scoring function must be sufficiently soft to dock unbound structures successfully. Some degree of surface overlap is tolerated to account for side-chain flexibility. Similarly for electrostatics, the interaction of the dispersed point charges of one protein with the Coulombic field of the other is measured rather than precise atomic interactions. We tested our docking protocol using the native rather than the complexed forms of the proteins to address the more scientifically interesting problem of predictive docking. In all but one of our test cases, correctly docked geometries (interface Calpha RMS deviation </=2 A from the experimental structure) are found during a global search of translational and rotational space in a list that was always less than 250 complexes and often less than 30. Varying degrees of biochemical information are still necessary to remove most of the incorrectly docked complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Animals
  • Antigen-Antibody Complex / chemistry
  • Computer Simulation
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzymes / chemistry
  • Enzymes / metabolism
  • Fourier Analysis
  • Humans
  • Macromolecular Substances*
  • Models, Molecular
  • Protein Binding
  • Protein Conformation*
  • Static Electricity


  • Antigen-Antibody Complex
  • Enzyme Inhibitors
  • Enzymes
  • Macromolecular Substances