Kinetic measurements of binding interaction with curvature evaluation
First Claim
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1. A method comprising:
- tracking the kinetics of a binding reaction to yield kinetics data;
fitting a time-profile curve to said kinetics data, said time-profile curve being characterized at least in part by a curvature-related value; and
evaluating the validity of said time-profile curve as a representative of said kinetics at least in part as a function of said curvature-related value.
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Abstract
Data from kinetic surface plasmon resonance measurements are fitted to time-profile curves. Time profile curves with sub-threshold curvature are flagged as being insufficient to provide reliable determinations of kinetic parameters and binding affinity. The remaining curves are used to calculate the kinetic parameters and binding affinity, obviating the need for multiple runs for these purposes. The resulting increase in throughput enables drug discovery methods in which kinetic measurements are performed earlier in the screening processes, e.g., so that all or most primary-screen hits can be subjected to data-rich kinetic measurements for screening purposes.
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Citations
20 Claims
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1. A method comprising:
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tracking the kinetics of a binding reaction to yield kinetics data; fitting a time-profile curve to said kinetics data, said time-profile curve being characterized at least in part by a curvature-related value; and evaluating the validity of said time-profile curve as a representative of said kinetics at least in part as a function of said curvature-related value. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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17. A system comprising:
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a sensor for monitoring the kinetics of a binding reaction to yield kinetics values; and a computer including software for gathering said kinetics values to yield a binding-versus-time profile, fitting a time-profile curve to said profile, determining a curvature-related value for said time-profile curve, and evaluating the validity of said time-profile curve as representative of said binding reaction at least in part as a function of said curvature-related value. - View Dependent Claims (18, 19, 20)
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Specification