A study of the structural correlates of affinity maturation: antibody affinity as a function of chemical interactions, structural plasticity and stability.
Mutations introduced in an antibody germline sequence as a result of somatic hypermutation could cause its derivatives to have an altered affinity for its target. Affinity maturation favors the selection of the antibodies which exhibit increased affinity. The mutations in 80 high affinity anti-thyroid peroxidase sequences derived from six germlines were analysed in terms of the physicochemical properties of the replacement residues, namely hydrophilicity, size and polarizability, and charge and polarity, in the context of its position and probable solvent accessibility. The effects of these substitutions were evaluated in terms of the resultant increased chemical interactivity potential of the affinity-matured antibodies relative to the germline. The results of the analysis would be useful in the rational design of antibodies and of other proteins for improved binding properties.
David
Maria Pamela C
MP
Virtual Laboratory of Biomolecular Structures, Marine Science Institute, College of Science, University of the Philippines Diliman, Quezon City 1101, Philippines. pamdavid@msi.upd.edu.ph
Asprer
Jonathan James T
JJ
Ibana
Joyce Sarah A
JS
Concepcion
Gisela P
GP
Padlan
Eduardo A
EA
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D000915:Antibody Affinity; D022801:Complementarity Determining Regions / Q000235:genetics; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D013329:Structure-Activity Relationship
D000906:Antibodies; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region