Seminar Causes and Consequences of Gross Inaccuracies in Binding and Potency Studies: Time to Act

Reliable decision-making in drug discovery, chemical biology, and diagnostic development depends on accurate measurements of molecular recognition and function. However, affinity and potency studies often treat imprecision (random error) as the main indicator of data quality, while overlooking inaccuracy (systematic bias). This seminar explains why standard assays for binding affinity (Kd), enzyme kinetics (Km), inhibition (Ki), and surrogate potency (IC50, EC50) can mask systematic deviations of orders of magnitude, even when curve fits appear acceptable and standard errors are small. Drawing on recent theoretical and experimental studies, it shows how the amplified propagation of concentration errors in nonlinear regression models can distort decisions in hit triage and candidate ranking. It also presents accessible browser-based tools for estimating the accuracy of Kd, Km, and related parameters from individual binding curves. Finally, the seminar outlines the goals of an emerging consortium that unites academic laboratories, instrumentation experts, and high-throughput screening developers to establish reliable experimental practices and consensus reporting standards.