The interactions Of alkali metal cations (M+ = Li+, Na+, K+, Rb+) with the amino acid cysteine (Cys) are examined in detail. Experimentally, bond energies are determined using threshold collision-induced dissociation of the W(Cys) complexes with xenon ill a guided ion beam mass spectrometer. Analyses of the energy dependent cross sections provide 0 K bond energies of 2.65 +/- 0.12. 1.83 +/- 0.05, 1.25 +/-0.03, and 1.06 +/- 0.03 eV for complexes of Cys with Li+, Na+, K+, and Rb+, respectively. All bond energy determinations include consideration Of unimolecular decay rates, internal energy of reactant ions, and multiple ion-molecule collisions. Ab initio calculations Lit the MP2(full)/6-311+G(2d,2p), B31-YP/6-311+G(2d,2p), and B3P86/63 11+G(2d,2p) levels with geometries and zero-point energies calculated Lit the B3LYP/6-311G(d,p) level for the lighter metals show good agreement with the experimental bond energies. For Rb+(Cys), similar calculations using the HW* basis set and ECP Underestimate the experimental bond energies, whereas the Def2TZVP basis set yields results in good agreement. Ground state conformers are tridentate for Li+ and Na+, and Subtle changes in the Cys side-chain orientation are found to cause noticeable changes in the alkali metal binding energy. For K+ and Rb+, tridentate and carboxylic acid bound (both charge-solvated and zwitterionic) structures are nearly isoenergetic, with different levels of theory predicting different ground conformers. The combination of this series of experiments and calculations; allows the influence of the sulfur functional group Of CYS Oil the overall binding strength to be explored. comparisons to previous results for serine elucidates the influence of sulfur for oxygen Substitution.