Evaluation of GRAMM low-resolution docking methodology on the hemagglutinin-antibody complex.

A single protein-protein pair, the complex of the influenza virus hemagglutinin with an antibody (Fab BH151), was suggested for prediction at the second experiment on the Critical Assessment of Techniques for Protein Structure Prediction. To predict the structure of the complex, we applied our docking program GRAMM at a decreased resolution (to accommodate the conformational inaccuracies). The lowest-energy match showed a remarkable "low-resolution" surface complementarity between the molecular structures. After receiving the experimental structure of the complex we had a chance to verify our assumptions and results. The analysis of the hemagglutinin-antibody interface revealed several significant conformational changes in the side chains, which resulted in deep interpenetrations of the hemagglutinin and the antibody structures. This confirmed our initial assumption that the structural changes will be beyond the tolerance of high-resolution rigid-body docking. The comparison of the predicted low-resolution match, submitted as the solution, and the experimentally determined complex showed significant structural discrepancies in the orientation of the antibody, due to the low-resolution character of the docking. Because of the severe structural errors, no residue-residue contacts were predicted correctly. However, a significant part of the antigenic site was determined. This illustrates the practical value of the present methodology for the initial prediction of the binding site, as well as points out the problem of transition from the low-resolution predictions of protein-protein complexes to the accurate structure.