Antibody structure, prediction and redesign

So far the difficulty to predict the structure of the third hypervariable loop of the heavy chain of antibodies has represented the main limitation in modelling the complete antigen binding site. We carefully analysed all available structures of immunoglobulins searching for rules relating the loop conformation to its amino acid sequence. Here, we analyse the conformation of this loop and show that we are able to predict the conformation of the ten residues proximal to the framework. The conformation of the remaining residues of loops longer than 10 residues can also be predicted in many cases. This, combined with the previously defined canonical structures for the other five hypervariable loops, is an important step toward the prediction of the complete immunoglobulin antigen-binding site. We exemplify our prediction protocol using three known immunoglobulin structures as test cases.