Prediction of the structure of a receptor–protein complex using a binary docking method

TO validate procedures of rational drug design, it is important to develop computational methods that predict binding sites between a protein and a ligand molecule. Many small molecules have been tested using such programs, but examination of protein–protein and peptide–protein interactions has been sparse. We were able to test such applications once the structures of both the maltosebinding protein1 (MBP) and the ligand-binding domain of the aspartate receptor2, which binds MBP, became available. Here we predict the binding site of MBP to its receptor using a 'binary docking' technique in which two MBP octapeptide sequences containing mutations that eliminate maltose chemotaxis are independently docked to the receptor. The peptides in the docked solutions superimpose on their original positions in the structure of MBP and allow the formation of an MBP–receptor complex. The consistency of the computational and biological results supports this approach for predicting protein–protein and peptide–protein interactions.