Docking of combinatorial peptide libraries into a broadly cross-reactive human IgM

A monoclonal IgM cryoglobulin with diverse binding behavior was isolated fr om a patient (Mez) with Waldenstrom's macroglobulinemia. It gave very high titers in the binding of combinatorially synthesized libraries of peptides ranging in size from two to eight residues. The crystal structure of Met Fv revealed that the binding site was divided into two cavities of unequal vo lumes with dimensions and chemical properties that were compatible with the binding of peptides, Access to this unique combination of structural infor mation and peptide binding data Led us to carry out Met-peptide docking sim ulations to gain insight into the Met binding propensities, In the present article, the results for docking of five peptide libraries are combined wit h discussions of the methods and approximations involved in the docking pro cess. We analyze the origins of peptide binding affinity for Met IgM in ter ms of its cross-reactivity and its structural preferences. Copyright (C) 20 01 John Wiley & Sons, Ltd.