1. Variations in Antigen−Antibody Association Kinetics as a Function of pH and Salt Concentration: A QSAR and Molecular Modeling Study
- Author
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Danièle Altschuh, Laurence Choulier, Erwin De Genst, Virginie Lafont, Annick Dejaegere, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Cellular and Molecular Immunology, Vrije Universiteit Brussel, and Klotz, Evelyne
- Subjects
Models, Molecular ,MESH: Hydrogen-Ion Concentration ,Molecular model ,[SDV]Life Sciences [q-bio] ,Molecular binding ,Quantitative Structure-Activity Relationship ,Antigen-Antibody Complex ,01 natural sciences ,Biochemistry ,Models ,MESH: Animals ,Salts/*chemistry ,Non-U.S. Gov't ,ComputingMilieux_MISCELLANEOUS ,MESH: Quantitative Structure-Activity Relationship ,0303 health sciences ,Antibodies/*chemistry/genetics/metabolism ,Chemistry ,Antigens/*chemistry/genetics/metabolism ,Temperature ,MESH: Antigen-Antibody Complex ,Hydrogen-Ion Concentration ,MESH: Temperature ,Receptor–ligand kinetics ,MESH: Salts ,MESH: Antigens ,Titration ,MESH: Models, Molecular ,Muramidase/chemistry/genetics/metabolism ,Protein Binding ,Quantitative structure–activity relationship ,Kinetics ,Thermodynamics ,Research Support ,010402 general chemistry ,MESH: Multivariate Analysis ,Antibodies ,03 medical and health sciences ,MESH: Protein Binding ,Animals ,Antigens ,030304 developmental biology ,MESH: Antibodies ,Solvation ,Molecular ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,0104 chemical sciences ,Crystallography ,Ionic strength ,MESH: Muramidase ,Multivariate Analysis ,Muramidase ,Salts ,Antigen-Antibody Complex/*chemistry - Abstract
0006-2960 (Print) Journal Article; The relationship between three environmental factors (ionic strength, pH, and temperature) and antigen-antibody binding kinetics was investigated using QSAR (quantitative structure-activity relationship) and molecular modeling approaches. The interaction used for this analysis is that between the camel antibody fragment cAbLys3 and lysozyme. Binding kinetics were measured using a Biacore 2000 instrument, at NaCl concentrations between 50 and 500 mM, at pH's between 5 and 10, and at temperatures between 15 and 30 degrees C, according to multivariate experimental designs. Variations in kinetic on- and off-rate parameters were up to 400- and 16-fold, respectively. Mathematical models that relate log k(on) to experimental conditions were developed. They indicated an influence of all three factors, with a clear dependency between pH and NaCl concentration for their effect on k(on). These models were able to predict on-rate parameters under new experimental conditions. Titration calculations using continuum electrostatics were performed on the crystallographic structures of the isolated and bound proteins to gain structural insight for the on-rate enhancement observed at pH
- Published
- 2005