Study On Sugar Structure Based On Quantum Chemistry Using Tree-step Computational Approach

The function of biomolecule is determined by its structure,that is,Biomolecule must be prepared with a specific spatial three-dimensional structure in the process of realizing its physiological functions.Information of its stable structure and the key influence of environment on their stability and transition are important first step in understanding the physical chemistry in vivo.As an important component of N-linked glycoproteins,the core pentasaccharide is often used as the model molecule for experiments and theoretical simulations.N-glycans are highly crucial to the potential application prospect of glycoprotein.However,its structural diversity and instability severely limit its further research.In this thesis,the structure of disaccharides and trisaccharides in N-glycans was constructed by tree-step computational approach,and the initial structure of disaccharides and trisaccharides were optimized by density functional theory combined with suitable quantum chemical basis groups.The stable configuration of those molecules with low-energy was obtained.The obtained configurations were analyzed by spectroscopy.Their structural characteristics were analyzed and summarized.On this basis,the core pentosaccharide were constructed by three ways.The constructed core pentosaccharide configuration was optimized to obtain a reasonable low-energy stable configuration.The main works of this theis are as followings.Firstly,the computational methods and software used in this thesis was introduced,including density functional theory,quantum chemistry calculation theory and first-principles calculation.Then,we apply the tree-step computational approach to investigate preferred structures of disaccharides with β-1,4-linked N-acetylglucosamine and D-mannose of corepentasaccharide in N-glycans.Due to the structural character of disaccharides,hydrogen bonds(H-bonds)are classified according to the upper and lower parts of GlcNAcβ(1,4)GlcNAc and Manβ(1,4)GlcNAc.Almost all building conformers are generated depending on the combination of H-bonds in the upper and lower parts,except for one conformer.After establishing initial configurations,theoretical simulations for optimization,preferred structures and frequency calculations are employed.Both energy and IR vibration signature are in good accord with the experimental and theoretical literature.Additionally,five new low-energy structures are found,which have not been reported by using the traditional conformational search.Secondly,structures of trimannose and mannose diacetylglucose trisaccharide were analyzed by tree-step computational approach,and their molecular configurations were constructed.Both energy and IR vibration signature are in good accord with the experimental and theoretical literature.Molecular configurations of core pentosaccharide were constructed successfully.In the subsequent calculations energy and spectrum,we found that the more comprehensive molecular configuration that compared with the results of traditional calculation with lower energy structure was obtained.