In this work,we developed the CHARMM all-atom force field parameters for the nonstandard biological residue chalcone,followed by the standard protocol for the CHARMM27 force field development.Target data were generate...In this work,we developed the CHARMM all-atom force field parameters for the nonstandard biological residue chalcone,followed by the standard protocol for the CHARMM27 force field development.Target data were generated via ab initio calculations at the MP2/6-31G* and HF/6-31G* levels.The reference data included interaction energies between water and the model compound F(a fragment of chalcone).Bond,angle,and torsion parameters were derived from the ab initio calculations and renormalized to maintain compatibility with the existing CHARMM27 parameters of standard residues.The optimized CHARMM parameters perform well in reproducing the target data.We expect that the extension of the CHARMM27 force field parameters for chalcone will facilitate the molecular simulation studies of the reaction mechanism of intramolecular cyclization of chalcone catalyzed by chalcone isomerase.展开更多
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...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。展开更多
基金National Institute of Biological Science, Beijing 102206,Chinasupported by the Major State Basic Research Development Programs of China(2011CBA00701)+3 种基金the National Natural Science Foundation of China(20973077,20973049)the Doctoral Fund of Ministry of Education of China(20112303110005)the Foundation for the Department of Education of Heilongjiang Province (1152G010,11551077)the Science Foundation for Leading Experts in Academe of Harbin of China(2011RFJGS026)
文摘In this work,we developed the CHARMM all-atom force field parameters for the nonstandard biological residue chalcone,followed by the standard protocol for the CHARMM27 force field development.Target data were generated via ab initio calculations at the MP2/6-31G* and HF/6-31G* levels.The reference data included interaction energies between water and the model compound F(a fragment of chalcone).Bond,angle,and torsion parameters were derived from the ab initio calculations and renormalized to maintain compatibility with the existing CHARMM27 parameters of standard residues.The optimized CHARMM parameters perform well in reproducing the target data.We expect that the extension of the CHARMM27 force field parameters for chalcone will facilitate the molecular simulation studies of the reaction mechanism of intramolecular cyclization of chalcone catalyzed by chalcone isomerase.
文摘建立含有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。
