An analysis of conformational changes on protein-protein association: implications for predictive docking

Conformational changes on complex formation have been measured for 39 pairs of structures of complexed proteins and unbound equivalents, averaged over interface and non-interface regions and for individual residues. We evalua te their significance by comparison with the differences seen in 12 pairs o f independently solved structures of identical proteins, and find that just over half have some substantial overall movement. Movements involve main c hains as well as side chains, and large changes in the interface are closel y involved with complex formation, while those of exposed non-interface res idues are caused by flexibility and disorder Interface movements in enzymes are similar in extent to those of inhibitors. All eight of the complexes ( six enzyme-inhibitor and two antibody-antigen) that have structures of both components in an unbound form available show some significant interface mo vement. However; predictive docking is successful even when some of the lar gest changes occur We note however that the situation may be different in s ystems other than the enzyme-inhibitors which dominate this study. Thus the general model is induced fit but, because there is only limited conformati onal change in many systems, recognition can be treated as lock and key to a first approximation.