MODELING PROTEIN DOCKING USING SHAPE COMPLEMENTARITY, ELECTROSTATICS AND BIOCHEMICAL INFORMATION

A protein docking study was performed for two classes of biomolecular complexes: six enzyme/inhibitor and four antibody/antigen. Biomolecula r complexes for which crystal structures of both the complexed and unc omplexed proteins are available were used for eight of the ten test sy stems. Our docking experiments consist of a global search of translati onal and rotational space followed by refinement of the best predictio ns. Potential complexes are scored on the basis of shape complementari ty and favourable electrostatic interactions using Fourier correlation theory. Since proteins undergo conformational changes upon binding, t he scoring function must be sufficiently soft to dock unbound structur es successfully. Some degree of surface overlap is tolerated to accoun t for sidechain flexibility. Similarly for electrostatics, the interac tion 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 comp lexed forms of the proteins to address the more scientifically interes ting problem of predictive docking. In all but one of our test cases, correctly docked geometries (interface C-alpha RMS deviation less than or equal to 2 Angstrom from the experimental structure) are found dur ing a global search of translational and rotational space in a list th at 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. (C) 1997 Academic Press Limited.