Abstract:
:The present article considers the influence of heterogeneity in a mobile analyte or in an immobilized ligand population on the surface binding kinetics and equilibrium isotherms. We describe strategies for solving the inverse problem of calculating two-dimensional distributions of rate and affinity constants from experimental data on surface binding kinetics, such as obtained from optical biosensors. Although the characterization of a heterogeneous population of analytes binding to uniform surface sites may be possible under suitable experimental conditions, computational difficulties currently limit this approach. In contrast, the case of uniform analytes binding to heterogeneous populations of surface sites is computationally feasible, and can be combined with Tikhonov-Phillips and maximum entropy regularization techniques that provide the simplest distribution that is consistent with the data. The properties of this ligand distribution analysis are explored with several experimental and simulated data sets. The resulting two-dimensional rate and affinity constant distributions can describe well experimental kinetic traces measured with optical biosensors. The use of kinetic surface binding data can give significantly higher resolution than affinity distributions from the binding isotherms alone. The shape and the level of detail of the calculated distributions depend on the experimental conditions, such as contact times and the concentration range of the analyte. Despite the flexibility introduced by considering surface site distributions, the impostor application of this model to surface binding data from transport limited binding processes or from analyte distributions can be identified by large residuals, if a sufficient range of analyte concentrations and contact times are used. The distribution analysis can provide a rational interpretation of complex experimental surface binding kinetics, and provides an analytical tool for probing the homogeneity of the populations of immobilized protein.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Svitel J,Balbo A,Mariuzza RA,Gonzales NR,Schuck Pdoi
10.1016/S0006-3495(03)75132-7subject
Has Abstractpub_date
2003-06-01 00:00:00pages
4062-77issue
6eissn
0006-3495issn
1542-0086pii
S0006-3495(03)75132-7journal_volume
84pub_type
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