otease-protein inhibitor and four antibody-antigen complexes. A large number of putative docked complexes have already been generated for the test systems using our rigid-body docking program, FTDOCK. They include geometries that closely resemble the crystal complex, and therefore act as a test for the renement procedure. In the protease-inhibitors, geometries that resemble the crystal complex are ranked in the top four solutions for four out of ve systems when solvation is included in the energy function, against a background of between 26 and 364 complexes in the data set. The results for the antibody-antigen complexes are not as encouraging, with only two of the four systems showing discrimination. It would appear that these results reect the somewhat different binding mechanism dominant in the two types of protein-protein complex. Binding in the protease-inhibitors appears to be "lock and key" in nature. The xed backbone and mobile side-chain representation provide a good model for

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We describe a novel computer system directed to evaluate protein complex formation in a liquid environment. The relevant feature of the system is a potential function expressing the main thermodynamic and kinetic factors leading to protein interaction in solution. The protein interaction model expresses the interaction energy as basically composed of three forces: electrostatic (hydrogen bond), van der Waals, and hydrophobic. The latter is defined in function of the forces that the solvent molecules exert on the surface of the complex, and the van der Waals forces between the monomers and the solvent. The interaction model implemented in the system has proven a high discrimination ability between different protein dockings, scoring high those close to the observed crystal structures. These results have led to the establishment of the basic principles underlying protein interaction, which constitutes the main way of expression of the biological function of these macromolecules. 1