Fits in a pocket: The binding mode of epothilone A (EpoA) to tubulin (see picture; rods: C gray, H white, N blue, O red, S yellow) is determined by NMR spectroscopy in aqueous solution. The results explain the existing structure–activity relationship data for epothilones with both native and mutant tubulins, and support the existence of a common pharmacophore for EpoA and paclitaxel.