The Accuracy Crisis in Binding and Potency Studies: Hidden Causes, Heavy Costs, and a Call to Act
Professor Sergey N. Krylov
Center for Research on Biomolecular Interactions, York University
Toronto, Canada
Tuesday, October 27, 2025
11:00 a.m.
In-person: C2-361
Abstract: Reliable decision-making in drug discovery, chemical biology, and diagnostics depends on accurate measures of molecular recognition and function. Yet our field often treats imprecision (random error) as the sole marker of data quality, while overlooking inaccuracy (systematic error). This seminar explains why standard assays for binding affinity (Kd), enzyme kinetics (Km), inhibition (Ki), and surrogate potency (IC50, EC50) can hide systematic deviations of two to three orders of magnitude, even when curve fits look acceptable and standard errors are small. Drawing on our recent theoretical and experimental studies [1–7], I will trace the main culprit—amplified propagation of concentration errors in nonlinear regression models—and show how it distorts structure–activity ranking, hit triage, and assay validation. Rapid, low-cost validation checks and a browser-based tool that estimates accuracy from individual binding curves will be demonstrated. Finally, I will outline the goals of the emerging Kd Accuracy Consortium, which brings together academic labs with instrumentation and HTS developers to set practical reporting standards. The session offers chemists and biochemists concrete steps to boost the credibility and fitness-for-purpose of binding and potency data.