Molecular forces in antibody maturation.
Analysis of x-ray crystal structures has clarified the nature of antibody-antigen interactions, and the conformational basis of specificity and affinity, but does not provide a clear picture of the dynamics of antigen recognition. In particular, we know that primary antibodies can bind a wider variety of ligands than their secondary counterparts--which are tuned for high specificity and affinity. Crystal structures show that in the absence of antigen the secondary antibody adopts a structure preformed for binding, but that the primary antibody does not. Our calculations show that the unligated state of the primary antibody has a well-defined structure, fluctuating no more widely than that of the secondary antibody, and undergoes a discrete structural rearrangement in response to ligand.
Demirel
Melik C
MC
College of Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Lesk
Arthur M
AM
D000906:Antibodies / Q000737:chemistry*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001666:Binding Sites, Antibody; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation
D000906:Antibodies