Conformation And Properties Of Amino Acid And Peptide Metalation

Protein is an important part of organisms and plays an extremely important rolein biological systems. The function of protein is closely related to its structure. Inorder to understand the structure and function of the protein, we must first understandthe structure and the properties of amino acid, and peptide. Therefore, the systematictheoretical calculations of amino acids and peptide conformation and the properties inthe gas phase and solution, can help people better understand and recognize the protein.Comprehensive theoretical study of L-threonine and L-allo-threonine and its ionin gas phase were carry out in this thesis. The H-bond types of the stable conformation,vibrationalspectraandthethermalpropertiesoftheprotonationanddeprotonationreac-tions,alsothe2stereoisomershydratedwithawatermoleculearecarriedout. Thestablecomplexes conformers of Cysteine with different metal ions were analysis. The resultsof the gas and Combined Discrete/SCRF Model are used for the activation mechanismof Oxytocin (OT) with metal ion. Comprehensive theoretical calculations of differentmetal ions activity order are discussed.In chapter 1, it outlines the basic theory of quantum mechanical calculations, andseveral quantitative methods, such as Hartree-Fock theory, Configuration Interaction,Many-Body Perturbation theory, Coupled Cluster Methods, Density Functional Theoryand Semi-empirical methods. The choice of basis sets are discussed. Also the solutionmodels used in this thesis are described. Finally, the software used in this thesis isdiscussed briefly.In chapter 2, we use ab initio methods and density functional theory to study thealiphatic threonine (Thr) structure and its thermal properties. Threonine molecule has 2asymmetric atoms (Cα, and Cβ), so there are 4 stereoisomers. In this chapter, the neu-tral, zwitterionic, protonated, deprotonated and secondary deprotonated conformationof the 2 L-configuration of stereoisomers (L-threonine and L-allo-threonine) were sys-tematicallyexplorethroughthepotentialenergysurface. ThethermalpropertiessuchasPA, PDE, GA and GB were also calculated. The H-bond types, vibrational spectra andthermal properties were analyzed. While taking into account the actual environment ofthe biological systems, a water molecule complex with threonine are also calculations.The characteristics of L-threonine and L-allo-threonine are analyzed based on their gasphase acidities, basicities, conformer energy differences and hydration positions. In chapter 3, conformers of cysteine and its complexes with alkali metal ion, alkaliearth metal ion are explored using density functional theory and MP2 method. Thegeometrical structures and thermal properties of cysteine complex with different metalions are discussed. The metal ions with larger ionic radius, and larger charge is morefavorable for salt bridge configuration (zwitterionic complexes) formation. It exist thezwitterioniccomplexationconformationwhencomplexwithmetalionsinthegasphase.The metal ion binding energies of Cysteine are increase with the charge, and increasewith the ionic radius in the same main group.In chapter 4, the structures of Oxytocin (OT) are explored using the density func-tional theory. The stable structure of the OT species in the gas phase and the aqueoussolution were searched through a large number of structures. Metal ion complexation(with Na⁺, K⁺, Ca²⁺, Zn²⁺, Ni²⁺, Mg²⁺ and Co²⁺ ) and protonated reactions are con-sidered. Drastic conformational changes were observed when OT was protonated ormetalated, which explains the biological activity of OT needs two divalent metal ions.DFT calculations of MIAs were also performed to explain the order of effectiveness ofdivalent metal ions, Co²⁺, Ni²⁺, Mg²⁺, Zn²⁺ and Ca²⁺, in promoting the interaction ofOT with its receptor.Chapter 5 provides a brief summary of the research results in the thesis.