Engineering antibody affinity and specificity.
A combination of ab initio calculations, "knowledge-based prediction", molecular graphics and site-directed mutagenesis has enabled us to probe the molecular details of antibody:antigen recognition and binding and to alter the affinity and specificity of an antibody for its antigen. The significance of electrostatic hydrogen bonding, hydrophilic/hydrophobic patch matching and van der Waals interactions as well as CDR:CDR interactions are discussed in relation to the results of site-directed mutagenesis experiments on the anti-lysozyme antibody Gloop2. The ability to generate reconstructed antibodies, chimeric antibodies, catalytic antibodies and the use of modelled antibodies for the design of drugs is discussed.
Webster
D M
DM
Laboratory of Molecular Biophysics, Oxford University, UK.
Roberts
S
S
Cheetham
J C
JC
Griest
R
R
Rees
A R
AR
D000818:Animals; D000915:Antibody Affinity; D000918:Antibody Specificity; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D009113:Muramidase / Q000276:immunology; D009154:Mutation; D015202:Protein Engineering; D051381:Rats
D009113:Muramidase