Abstract
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‐dimensional
Ab
antibody
A
absorbance
C
constant
CDR
complementarity‐determining region
CH
constant domain of the heavy chain
ELISA
enzyme‐linked immunosorbent assay
Fv
fragment variable
H
heavy
HB
hydrogen bond
L
light
PDB
Protein Data Bank
V
variable
VH
variable region of the heavy chain
VL
variable region of the light chain
vdW
van der Waals