Ion mobility spectrometry (IMS) has recently been established as a powerful tool to separate the protease digest mixtures and identify their peptide components. As accurate calculation of mobilities is critical for this technique, a new rapid method based on intrinsic size parameters (ISPs) of amino acid residues has been devised. However, those parameters had to be obtained by tedious statistical analysis of a large body of experimental data. Here we demonstrate that they can instead be derived a priori, based on the stoichiometry of a residue. Our main finding is that the ISP of a residue is essentially determined by its density, that is, the average mass/size ratio of its constituent atoms. This is in accordance with an interpretation in which peptides assume compact conformations in the gas phase dominated by the solvation of ionic charge.