Development of the Free energy Calculation method and the Construction of Carbohydrate Structure Library

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We have been investigating the confirmation of the carbohydrates in solution by using molecular dynamics simulation. In order to obtain the fine energy of the conformational change in solution, we applied the umbrella sampling method to charmm program. We obtained the Ramachandran free energy map of the conformational potential mean force for neocarrabiose in water. The potential energy map showed the different behavior compared with that of calculated in a previous study for this molecule in vacuum. This method was tried to apply to other carbohydrates in solution, such as oligosaccharide in immunoglogrin G.Carbohydrates in glycoprotein attract a great deal of attention because the glycan chains are suggested to play a variety of biological functions. However, the details of the role of glycan chains have not fully understood yet. Immunoglobulin G (IgG) is known to form antigen-antibody complex and it further bind to the receptors (FcR) for the Fc portion of IgG.. Nose and Wigzell com … More pared the IgG antibodies with or without carbohydrate chains and showed that the carbohydrate-deficient IgG will lead to an inability of the antibodies to interact with FcR on macrophages. Kato performed NMR experiment and suggested that the Fc portion takes different conformation between the conditions with or without glycan chains. In order to investigate the role of glycan chain more precisely, molecular dynamics simulation of the Fc portion of IgG was performed. The structure of the Fc portion of IgG was constructed from the crystal structure of Harris, et. Al. by removing the Fab fragments. Although the calculation with explicit water molecules is crucial in a proper treatment of biopolymers in aqueous solution, such calculation is too expensive in this case. Therefore, we first tried to perform the molecular dynamics simulation by using simple method, which mimic the solvent effect, such as high dielectric constant and generalized Born method. As a basic information for this work, we calculated the ramachandran potential surface map for disaccharides which constructs the IgG oligosaccharide.We further studied the basic interaction exists in the carbohydrate-carbohydrate and carbohydrate-protein complexes, such as CH-p interaction. Ring interconversion of the glucopyranose ring was also investigated by using ab initio calculation. The results showed that the E_3 conformation was found to be a transition state of the ring interconversion. Intrinsic reaction coordinate (IRC) calculations indicated that the E_3 conformation is a transition state of the ring interconversion path from ^4C_1 to B_3,o via E_3 conformation. Less