A theoretical study of potassium cation binding to glycylglycine (GG) and alanylalanine (AA) dipeptides.

By combining Monte Carlo conformational search technique with high-level density functional calculations, the geometry and energetics of K(+) interaction with glycylglycine (GG) and alanylalanine (AA) were obtained for the first time. The most stable K(+)-GG and K(+)-AA complexes are in the charge-solvated (CS) form with K(+) bound to the carbonyl oxygens of the peptide backbone, and the estimated 0 K binding affinities (DeltaH(0)) are 152 and 157 kJ mol(-1), respectively. The K(+) ion is in close alignment with the molecular dipole moment vector of the bound ligand, that is, electrostatic ion-dipole interaction is the key stabilizing factor in these complexes. Furthermore, the strong ion-dipole interaction between K(+) and the amide carbonyl oxygen atom of the peptide bond is important in determining the relative stabilities of different CS binding modes. The most stable zwitterionic (ZW) complex involves protonation at the amide carbonyl oxygen atom and is approximately 48 kJ mol(-1) less stable than the most stable CS form. The usefulness of proton affinity (PA) as a criterion for estimating the relative stability of ZW versus CS binding modes is examined. The effect of chain length and the nature of metal cations on cation-dipeptide interactions are discussed. Based on results of this study, the interaction of K(+) with longer peptides consisting of aliphatic amino acids are rationalized.

Absolute potassium cation affinities (PCAs) in the gas phase.

The potassium cation affinities (PCAs) of 136 ligands (20 classes) in the gas phase were established by hybrid density functional theory calculations (B3-LYP with the 6-311+G(3df,2p) basis set). For these 136 ligands, 70 experimental values are available for comparison. Except for five specific PCA values-those of phenylalanine, cytosine, guanine, adenine (kinetic-method measurement), and Me(2)SO (by high-pressure mass spectrometric equilibrium measurement)-our theoretical estimates and the experimental affinities are in excellent agreement (mean absolute deviation (MAD) of 4.5 kJ mol(-1)). Comparisons with previously reported theoretical PCAs are also made. The effect of substituents on the modes of binding and the PCAs of unsubstituted parent ligands are discussed. Linear relations between Li+/Na+ and K+ affinities suggest that for the wide range of ligands studied here, the nature of binding between the cations and a given ligand is similar, and this allows the estimation of PCAs from known Li+ and/or Na+ affinities. Furthermore, empirical equations relating the PCAs of ligands with their dipole moments, polarizabilities (or molecular weights), and the number of binding sites were established. Such equations offer a simple method for estimating the PCAs of ligands not included in the present study.