A Study Of Density Functional Theory And Molecular Dynamics Simulation On The Association And Hydration Of Alanine In Saline Solution

Metal ions are widely involved in the life process, the interactions between metal ions and amino acids or proteins molecules play an important role in many biological functions. At present, most diseases which is difficult to cure in clinical are also related to the anomaly combination of amino acids and some metal ions. Therefore, the investigation on the interaction between amino acids and metal ions in aqueous solution has the vital significance for the further study of polypeptide, protein, and the interpretation of some life phenomena. The related behavior of amino acids and metal ions in aqueous solution has been studied by a large amount of experimental and theoretical research. But the interpretation of the molecular mechanism still need to be improved. Therefore, it is necessary to further investigate the association characteristics of amino acid molecular in saline solution.In this paper, associated structures of alanine molecule, and the interaction structure of alanine and Na+, Cu2+, Zn2+ and Cl- was investigated using CAM-B3 LYP method and the classical molecular dynamics(MD) simulation. Based on results of CAM-B3 LYP calculations and MD simulations, the effect of ion hydration on the interaction between metal ion and alanine polar groups was analysed, and thus the effect of the interaction between metal ions or Cl- and alanine polar groups on the association of alanine in aqueous solution was disscussed. And the following results were be drawn accordingly:In the gas phase, the association structures of alanine molecules has two typical isomers, bidentate association structure, and doubly chelated association structure of alanine molecules which is much more stable, and the energy difference between these two isomers is 68 k J/mol. Calculated binding energies indicate that the bidentate coordination form between Na+, Cu2+, Zn2+ and alanine carboxyl is more stable. Cl- can form ionic hydrogen bond(i HB) with hydrogen atom of the amino group. The interactions between alanine and Cl- or cations are all stronger than the association between alanine molecules, especially the divalent metal ions Cu2+ and Zn2+. The interaction between Cl- and alanine is relatively weak, but it is still strong than that between alanine molecules. Our calculated results show that the ion hydration is relatively strong, especially for the two divalent cations. This means that, the ion hydration and the associations between ions and polar groups of alanine will compete with each other in aqueous solution, and such competion will affect the association between amino acid molecules. The results of NBO charge population analyses show that the interaction structures between alanine polar group and metal ions or Cl- will result in the polar group being more positive or negatively, respectively. There is obvious charge transfer between the divalent metal cations and the alanine carboxyl group, and the charge transfer effect between Cl- and amino group is less obvious.Results of classical molecular dynamics simulation showed that the zwitterionic alanines have two associative structures, monodentate and bidentate. In saline solution, the interaction between anion, cations and alanine polar group, and those interactions will hinder the association of alanine molecules in some extent. The interaction of cation with alanine, not only weakens the association between alanine molecules, but also results in the transformation between two typical conformations of associated alanine molecules. Kinds of ions, concentration of ions will both affect the associated conformation between cation/anion and alanine, and the degree of association between alanine molecules. Compared with that the association between metal ions, the interaction between Cl- and alanine amino group is weak, and the effect on the association of alanine molecules is relatively small. In dilute aqueous solution of Zn Cl2, the interaction between Zn2+ and the carboxyl group of alanine molecule is separated by the first hydration shell of Zn2+, in similar form of solvent shared ion pair. In concentrated Zn Cl2 aqueous solution, Zn2+ directly contact with carboxyl of alanine molecule, and thus the effect on alanine association is obvious.