Title :
Estimation of kinetic rate constants from surface plasmon resonance experiments
Author :
Evans, Neil D. ; Lowe, Daniel ; Briggs, David ; Higgins, R. ; Bentall, Andrew ; Ball, S. ; Mitchell, David ; Zehnder, Daniel ; Chappell, Michael J.
Author_Institution :
Sch. of Eng., Univ. of Warwick, Coventry, UK
Abstract :
In order to characterise antibody binding characteristics it is necessary to determine reaction constants from quantitative measurements of the process. Surface plasmon resonance (SPR) provides convenient real-time measurement of the reaction that enables subsequent estimation of the reaction constants. Two models are considered that represent the binding reaction in the presence of transport effects. One of these models, the effective rate constant approximation, can be derived from the other applying a quasi-steady state assumption. Uniqueness of the reaction constants with respect to SPR measurements is considered via a structural identifiability analysis. It is shown that the effective rate constant model is unidentifiable, unless the analyte concentration is known, while the full model is structurally globally identifiable provided association and dissociation phases are considered. Both models provide comparable estimates for the unknown rate constants for a commercial anti-A monoclonal IgM experiment.
Keywords :
approximation theory; association; biochemistry; dissociation; identification; molecular biophysics; parameter estimation; proteins; reaction rate constants; surface plasmon resonance; SPR measurements; analyte concentration; antibody binding characteristics; association phase; binding reaction; commercial anti-A monoclonal IgM experiment; dissociation phase; kinetic rate constant estimation; quasisteady state assumption; rate constant approximation; rate constant model; reaction constant determination; reaction constant estimation; real-time reaction measurement; structural identifiability analysis; structurally globally identifiable model; surface plasmon resonance experiments; transport effects; Biomedical systems; binding affinity; parameter estimation; structural identifiability; surface plasmon resonance; surface-volume reactions;
Conference_Titel :
Control 2010, UKACC International Conference on
Conference_Location :
Coventry
Electronic_ISBN :
978-1-84600-038-6
DOI :
10.1049/ic.2010.0300