含有L-对硝基苯丙氨酸的BAFF改构体的分子动力学模拟与分析

发布时间：2018-06-13 17:43

本文选题：纳米分子动力学(NAMD) + 可视化分子动力学(VMD)　；参考：《中国药科大学学报》2017年02期

【摘要】：建立含有L-对硝基苯丙氨酸(p-nitro-L-phenylalanine,pNO_2Phe)蛋白的分子动力学模拟方法,分析了含有pNO_2Phe的蛋白具有免疫原性的构效关系,为其他含有非天然氨基酸蛋白的动力学模拟研究提供参考。使用CGenFF-paramchem计算天然氨基酸中不存在的L-对硝基苯丙氨酸的新的成键、键角、二面角信息与能量,将新成键的键长、键角、二面角参数与相应的能量信息写入CHARMM(chemistry at Harvard macromolecular mechanics)力场参数文件中。重新定义L-对硝基苯丙氨酸的CHARMM力场参数后,利用纳米分子动力学(NAMD)成功对含有L-对硝基苯丙氨酸的B淋巴细胞刺激因子(BAFF)进行动力学模拟。统计动力学模拟过程中的每一帧体系的温度,作出的温度分布图符合正态分布,证明了新定义力场参数的稳定性。模拟结果中,蛋白的均方根偏差(RMSD)在趋近于2.5,pNO_2Phe残基的均方根涨落(RMSF)为3.7,显著高于分子的其他部位,表明pNO_2Phe残基运动剧烈,蛋白在该残基附近结构的可变性较大,可能会产生新的构象表位,为含有pNO_2Phe蛋白成为自体疫苗的设计提供了理论上的可行性。
[Abstract]:A molecular dynamics simulation method containing p-nitro-L-phenylalanine (p-nitro-L-phenylalanine) protein was established, and the immunogenicity of the protein containing pNO2Phe was analyzed, which provides a reference for the kinetic simulation of other non-natural amino acid proteins. Using CGenFF-paramchem to calculate the new bond, bond angle, dihedral angle and energy of L- p-nitrophenylalanine, which does not exist in natural amino acids, the new bond length, bond angle, The dihedral angle parameter and the corresponding energy information are written into the force field parameter file of CHARMMMU chemistry at macromolecular mechanisms. After redefining the CHARMM force field parameters of L- p-nitrophenylalanine, the kinetics of B lymphocyte stimulating factor (BAFF) containing L- p-nitrophenylalanine was successfully simulated by nano molecular dynamics (NAMD). The temperature distribution diagram of each frame system in the process of statistical dynamics simulation accords with the normal distribution, which proves the stability of the newly defined force field parameters. In the simulated results, RMSD) of the RMSD of the protein approaching to 2.5pNO2Phe residue was 3.7, which was significantly higher than that of the other parts of the molecule, indicating that the movement of the PNO2Phe residue was intense, and the structure of the protein near the residue was more changeable, and the RMSF of the protein was higher than that of the other parts of the molecule, which indicated that the RMSD of the protein was significantly higher than that of the other parts of the molecule. A new conformational epitope may be produced, which provides theoretical feasibility for the design of autogenous vaccine containing pNO2Phe protein.
【作者单位】：中国药科大学生命科学与技术学院;
【基金】：国家教育部博士点基金资助项目(No.20120096110007) 国家自然科学基金资助项目(No.81273426)~~
【分类号】：R392

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