Model and simulation of multivalent binding to fixed ligands.
A model to quantitate the principal aspects of multivalent binding was developed. It describes the random distribution of an immobilized component (the ligand) taking into account local densities. The binding of a bivalent molecule (the analyte) to the ligand is described as occurring in two steps, the second of which is driven by the local concentration of neighboring ligands. The model was used to simulate the kinetics of bivalent binding in surface plasmon resonance biosensors such as BIAcore. The simulations are compared with measured data. The simulation quantitates the influence of bivalent binding on the sensor signal, as a function of ligand density, analyte concentration, and binding site distance. Such simulations will be helpful for understanding and designing experiments to assess avidity effects as well as for developing molecules with high avidity. Furthermore, they help to analyze the inherent complexity in seemingly simple sensorgrams.
Müller
K M
KM
Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, Zürich, CH-8057, Switzerland.
Arndt
K M
KM
Plückthun
A
A
D000915:Antibody Affinity; D015374:Biosensing Techniques; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D013499:Surface Properties
D008024:Ligands