Beyond Km and Vmax: a geometric framework for characterizing enzyme modulation and validating kinetic data

This deposit contains the calculation template and supporting materials for the geometric ("catalytic vector") framework described in the manuscript "Beyond Km and Vmax: a geometric framework for characterizing enzyme modulation and validating kinetic data" (J. Salerno, Università degli Studi di Firenze). The framework represents the catalytic state of a Michaelis–Menten enzyme as a point in the normalized (Km, Vmax) plane, so that ligand-induced modulation becomes a measurable geometric displacement. Each state is described by dimensionless descriptors — a catalytic angle, vector norm, and circle and triangle areas — whose native values are universal constants. A four-level algorithm then classifies every perturbation by biological direction (activation, inhibition, or indeterminate), intensity, absolute-impact alert, and dominant kinetic mechanism (Km-dominant vs Vmax-dominant). The framework was validated retrospectively against twenty compounds spanning three independent enzyme systems (CYP3A4, monoamine oxidase B, and arginase) and the full range of modulation patterns, from allosteric activation to time-dependent inhibition. Its assignments reproduced the mechanisms declared in the source literature in every known-mechanism case, resolved detail beyond the original analyses — including a concentration-dependent shift in dominant axis (perillyl alcohol) and the opposite regio-selective action of a single effector on two parallel metabolic routes of the same substrate (Shenmai injection on midazolam 1'- and 4-hydroxylation) — and correctly withheld classification under weak, sub-threshold modulation (arginase peptides, negative control). Contents: CYP_template_EN_FIXED_S2.xlsx: the complete Excel calculation template, including all compound sheets, the raw-data table with sources and units (Table S1), and the threshold-sensitivity analysis (Table S2). GeoGebra_Interactive_Constructions.txt: links to the interactive dynamic-geometry constructions (GeoGebra) that allow the reader to vary the effector concentration and observe the geometric response in real time. The associated manuscript has been submitted for peer review. This deposit provides the data and tools supporting the study.