Background: Protein-protein docking is an in silico method to predict the formation of protein complexes. Due to limited computational resources, the docking approach has been developed under the assumption of rigid docking, in which one of the two protein partners remains rigid during the protein associations and water contribution is ignored or implicitly presented. While the rigid docking has successfully predicted structures of various protein complexes, it seems to-date that most docking algorithms often fail to discriminate the correct predictions from the false positives, especially for Antigen/Antibody complexes. 

To tackle this issue, a new energy-based scoring function is proposed in this paper, namely IFACEwat – a combined Interface Atomic Contact Energy (IFACE) and water effect, to re-rank results of a rigid docking algorithm and therefore further improve the discrimination of the near-native structures from the false positives, especially for Antigen/Antibody complexes. Unlike other re-ranking techniques, the IFACEwat explicitly implements interfacial water into the protein interfaces to account for the water-mediated contacts during the protein interactions.

Results: Our results showed that the IFACEwat increased both the numbers of the near-native structures and improved their ranks as compared to the initial rigid docking. In fact, the IFACEwat achieved a success rate of 83.8% for Antigen/Antibody complexes, 92.3% and 90% respectively for medium and difficult cases of protein complexes. 

Conclusion: The improvement is achieved by explicitly taking into account the contribution of water during the protein interactions, which was ignored or not fully presented by the initial rigid docking and other re-ranking techniques. In addition, the IFACEwat maintains sufficient computational efficiency of the initial docking algorithm, yet improves the ranks as well as the number of the near native structures found.