Search strategies and evaluation in protein-protein docking: principles, advances and challenges

Protein-protein docking is attracting increasing attention in drug discovery research targeting protein-protein interactions, owing to its potential in predicting protein-protein interactions and identifying 'hot spot' residues at the protein-protein interface. Given the relative lack of information about binding sites and the fact that proteins are generally larger than ligand, the search algorithms and evaluation methods for protein-protein docking differ somewhat from those for protein-ligand docking and, hence, require different research strategies. Here, we review the basic concepts, principles and advances of current search strategies and evaluation methods for protein-protein docking. We also discuss the current challenges and limitations, as well as future directions, of established approaches.