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Docking of combinatorial peptide libraries into a broadly cross‐reactive human IgM
Author(s) -
Yuriev Elizabeth,
Ramsland Paul A.,
Edmundson Allen B.
Publication year - 2001
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.533
Subject(s) - docking (animal) , peptide , binding site , chemistry , plasma protein binding , computational biology , biochemistry , combinatorial chemistry , stereochemistry , biology , medicine , nursing
A monoclonal IgM cryoglobulin with diverse binding behavior was isolated from a patient (Mez) with Waldenström'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 Mez Fv revealed that the binding site was divided into two cavities of unequal volumes with dimensions and chemical properties that were compatible with the binding of peptides. Access to this unique combination of structural information and peptide binding data led us to carry out Mez‐peptide docking simulations to gain insight into the Mez binding propensities. In the present article, the results for docking of five peptide libraries are combined with discussions of the methods and approximations involved in the docking process. We analyze the origins of peptide binding affinity for Mez IgM in terms of its cross‐reactivity and its structural preferences. Copyright © 2001 John Wiley & Sons, Ltd.Abbreviations used : 3‐D three‐dimensionalAb antibodyA absorbanceC constantCDR complementarity‐determining regionCH constant domain of the heavy chainELISA enzyme‐linked immunosorbent assayFv fragment variableH heavyHB hydrogen bondL lightPDB Protein Data BankV variableVH variable region of the heavy chainVL variable region of the light chainvdW van der Waals