Determination of the 3D structures … … of large molecules challenges spectroscopy to perform better. In their Communication on page 6002 ff. O. V. Boyarkin et al. use IR–UV double-resonance cold-ion spectroscopy for conformational assignment of the electronic spectra of a protonated decapeptide and for measurements of absolute absorption cross-sections of vibrational transitions in this species. The limitations of the IR–UV double-resonance approach are illustrated by measuring the gas-phase IR spectrum of a cold, protonated intact protein.