title: Optimal design for the dose-response screening of tight-binding enzyme inhibitors.
abstract: Optimal experimental designs for the dose-response screening of enzyme inhibitors were studied within the framework of the Box-Lucas theory. If the enzyme concentration E is considered as a fixed constant, an exact two-point D-optimal design consists of a pair of inhibitor concentrations equal to I(1)=0 and I(2)=E+K, where K is the apparent inhibition constant. If the enzyme concentration is treated as an adjustable parameter, an empirical three-point D-optimal design consists of three inhibitor concentrations equal to I(1)=0, I(2)=E+3K, and I(3)=0.7E. These results were applied to design optimized, irregularly spaced concentration series for routine inhibitor screening. A heuristic Monte Carlo simulation study confirmed that the optimized dilution series is significantly more efficient than the classic series characterized by a constant dilution ratio. An online calculator to create optimized dilution series is freely available at http://www.biokin.com/design/.
authors.affiliation: BioKin Ltd., Watertown, MA 02472, USA. pksci01@biokin.com
authors.forename: Petr
authors.initials: P
authors.lastname: Kuzmič
mesh_terms: D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology*; D007700:Kinetics; D008954:Models, Biological; D009010:Monte Carlo Method; D012107:Research Design
chemical_list: D004791:Enzyme Inhibitors