A Database of Transition-Metal-Coordinated Peptide Cross-Sections: Selective Interaction with Specific Amino Acid...

Ion mobility mass spectrometry (IMS-MS) techniques were used to generate a database of 2288 collision cross sections of transition-metal-coordinated tryptic peptide ions. This database consists of cross sections for 1253 [Pep + X]²⁺ and 1035 [Pep + X + H]³⁺, where X²⁺ corresponds to Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺, or Zn²⁺. This number of measurements enables the extraction of structural trends for transition-metal-coordinated peptide ions. The range of structures and changes in collision cross sections for X²⁺-coordinated species (compared with protonated species of the same charge state) is similar to Mg²⁺-coordinated species. This suggests that the structures are largely determined by similarities in cation size with differences among the cross section distributions presumably caused by X²⁺ interactions with specific functional groups offered by the residue R-groups or the peptide backbone. Cross section contributions for individual residues upon X²⁺ solvation are assessed with the derivation of intrinsic size parameters (ISPs). The comparison of the [Pep + X]²⁺ ISPs with those previously reported for [Pep + Mg]²⁺ ions displays a lower contribution to the cross section for His, carboxyamidomethylated Cys, and Met, and is consistent with specific metal-residue interactions identified within protein X-ray crystallography databases. Graphical Abstract ᅟ.