The interactions of rubidium and cesium cations with four amino acids (AA) including methionine (Met), phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp) are examined in detail. Experimentally, the bond dissociation energies (BDEs) are E determined using threshold collision-induced dissociation of the Rb+(AA) and Cs+(AA) complexes with xenon in a guided ion beam tandem mass spectrometer. Analyses of the energy dependent cross sections include consideration of unimolecular decay rates, internal energy of the reactant ions, and multiple ion-neutral collisions. 0 K BDEs of 121.0 +/- 7.0 (102.8 +/- 6.6), 123.8 +/- 7.2 (112.9 +/- 5.5), 125.8 +/- 7.4 (115.6 +/- 6.9), and 138.1 +/- 7.5 (125.0 +/- 6.8) kJ/mol are determined for complexes of Rb+ (Cs+) with Met, Phe, Tyr, and Trp, respectively. Quantum chemical calculations are conducted at the B3LYP, MP2(full), and M06 levels of theory with geometries and zero point energies calculated at the B3LYP level using def2-TZVPPD basis sets. Results obtained using all three levels show good agreement with experiment, with B3LYP values being systematically low and MP2(full) and M06 values being systematically high. At 0 and 298 K, theory predicts the ground state conformers for M+(Met) either have tridentate binding of the metal cation to the carbonyl, amino, and sulfur groups (MP2 and M06) or to both oxygens of a zwitterionic conformation (B3LYP). At 298 K, binding to the carboxylic acid group and the sulfur also becomes competitive. For the aromatic amino acids at 0 K, most levels of theory favor tridentate binding of the metal ions to the backbone carbonyl and amino groups along with the pi-cloud of the ring, whereas for Rb+(Trp) and Cs+(AA), B3LYP theory favors binding to only the carbonyl and ring groups. At 298 K, B3LYP favors the latter binding mode for all three Rb+(aromatic AA) complexes. Comparison of these results to those for the smaller alkali cations provides insight into the trends in binding affinities and structures associated with metal cation variations.