Theoretical Studies On The Interactions Of Amino Acids With Calciumion

In living organisms, the complexation of metal cations to amino acid is one ofthe most important processes, especially for Ca²⁺. The binding of amino acid with²⁺is involved in a large number of different physiological reactions taking place inall forms of life （ie., flagella movement, intracellular signaling, the complementsystem, blood coagulation, muscle contraction, and neurotransmitter release insynapses）. The knowledge of the binding interactions of the Ca²⁺and amino acidsystems is important to predict where the calcium ion attachment occurs preferentiallyin a macromolecule and how strong the binding at a particular site.（1） By surveying the possible permutations of metal chelation and hydrogenbonding, a number of initial structures for the calcium–amino acids complexes, eachof them with maximum number of hydrogen bonds, were generated. All the structureswere initially optimized with the Tight-Binding method, and then optimized byhigher-level MP2/6-31G（d,p） method. For the gas-phase low-energy structures, thesingle-point energies were calculated at MP2/6-311++G（d,p）. All the calculations atthe MP2level were performed using the Gaussian03package. We showed that in thegas phase the salt-bridge structure is the most preferred Ca²⁺binding motif foraliphatic amino acids with no heteroatom in the side chain, while for other aminoacids they have charge-solvated structure except for glutamic acid, glutamine,arginine, lysine and tryptophane. IR spectra of Gln-Ca²⁺and Asn-Ca²⁺complexeswere calculated and compared well with the available experiments.（2） Majority of biological processes occurs in aqueous environments and water molecules play a central role by moderating electrostatic forces. In our present study,NBO analysis, geometry optimizations and single point energies were also conductedin the PCM model at the same level using the Gaussian03package with a dielectricconstant of78.39（water）. In addition, the vertical excitation energies were computedusing the time-dependent density functional theory （TDDFT） method at theB3LYP/6-311++G（d,p） level. The bidentate salt-bridge structure was determined tobe the most favorable for all the twenty kinds of amino acids by chelation of Ca²⁺toboth oxygen atoms of the negatively carboxylate group in the backbone. The muchlower magnitude of charge transfer contribution （about0.1e） in calcium ioncoordinated complexes suggests that the interactions in these complexes areelectrostatic, which can also be shown by the very tiny wiberg bond indices. Thevertical excitation energies of the calcium ion-aromatic amino acid compounds havebeen discussed, the blue-shifts have been found for Phe-Ca²⁺and Trp-Ca²⁺, but thepeculiar red-shift has been found for Tyr Ca²⁺, possibly because the p-conjugatedegree of hydroxyl with aromatic ring is enhanced by NH3+above the ring.（3） Compared with the full solution studies, the gas-phase studies of hydratedclusters can provide much detailed insights into thermochemical and structuralchanges with the stepwise addition of water molecules in the first shell of biologicalmolecules. The structural changes triggered by hydration and the binding energies ofhydrated composites were studied for the three hydrated molecular clusters includingGly-Ca²⁺（H₂O）n, Thr-Ca²⁺（H₂O）nand Phe-Ca²⁺（H₂O）nat the MP2/6-311++G（d,p）level. In the investigation on the hydration of all the three systems, the clusters withthe first hydration shell displaying an octacoordination configuration around calciumion are found to be most competitive in binding energy no matter for aromatic aminoacid clusters Phe-Ca²⁺（H₂O）nor the aliphatic amino acid clusters Gly-Ca²⁺（H₂O）nandThr-Ca²⁺（H₂O）n. The bond lengths and bond angles of the above-mentioned structuresare close to the corresponding values from the PCM calculations. Water moleculeshave a considerable effect on the relative stability of individual complexes, withbinding energy decreasing in the order Phe-Ca²⁺> Thr-Ca²⁺> Gly-Ca²⁺without waterand Thr-Ca²⁺（H₂O）n> Phe-Ca²⁺（H₂O）n> Gly-Ca²⁺（H₂O）nupon hydration, respectively. Owning to the different nature of side chain of Gly, Thr and Phe, variousintermolecular hydrogen bonds appear in the three hydrated composites, which giverise to different vibrational absorption peaks.