Considerations for improved performance of competition association assays analysed with the Motulsky-Mahan's "kinetics of competitive binding" model.

ABSTRACT:

Background and purpose

Target engagement dynamics can influence drugs' pharmacological effects. Kinetic parameters for drug:target interactions are often quantified by evaluating competition association experiments-measuring simultaneous protein binding of labelled tracers and unlabelled test compounds over time-with Motulsky-Mahan's "kinetics of competitive binding" model. Despite recent technical improvements, the current assay formats impose practical limitations to this approach. This study aims at the characterisation, understanding and prevention of these experimental constraints, and associated analytical challenges.

Experimental approach

Monte Carlo simulations were used to run virtual kinetic and equilibrium tracer binding and competition experiments in both normal

SUBMITTER: Georgi V 

PROVIDER: S-EPMC7029771 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature