NAMD是美国伊利诺伊大学厄本纳-香槟分校(University of Illinois at Urbana-Champaign,UIUC)开发的著名大规模分子动力学并行计算软件包,NAMD是当前用来在分子水平上进行生命过程模拟研究的主要软件之一。我们在中国科学院计算机网络...NAMD是美国伊利诺伊大学厄本纳-香槟分校(University of Illinois at Urbana-Champaign,UIUC)开发的著名大规模分子动力学并行计算软件包,NAMD是当前用来在分子水平上进行生命过程模拟研究的主要软件之一。我们在中国科学院计算机网络信息中心的"深腾7000"百万亿次超级计算机上进行了移植和优化,并对STMV典型的烟草花叶卫星病毒进行了2048处理器核的模拟计算,计算测试表明取得了较好的加速效果。展开更多
The parallel scaling (parallel performance up to 48 cores) of NAMD package has been investigated by estimation of the sensitivity of interconnection on speedup and benchmark results—testing the parallel performance o...The parallel scaling (parallel performance up to 48 cores) of NAMD package has been investigated by estimation of the sensitivity of interconnection on speedup and benchmark results—testing the parallel performance of Myrinet, Infiniband and Gigabit Ethernet networks. The system of ApoA1 of 92 K atoms, as well as 1000 K, 330 K, 210 K, 110 K, 54 K, 27 K and 16 K has been used as testing systems. The Armenian grid infrastructure (ArmGrid) has been used as a main platform for series of benchmarks. According to the results, due to the high performance of Myrinet and Infiniband networks, the ArmCluster system and the cluster located in the Yerevan State University show reasonable values, meanwhile the scaling of clusters with various types of Gigabit Ethernet interconnections breaks down when interconnection is activated. However, the clusters equipped by Gigabit Ethernet network are sensitive to change of system, particularly for 1000 K systems no breakdown in scaling is observed. The infiniband supports in comparison with Myrinet, make it possible to receive almost ideally results regardless of system size. In addition, a benchmarking formula is suggested, which provides the computational throughput depending on the number of processors. These results should be important, for instance, to choose most appropriate amount of processors for studied system.展开更多
The comparable feature analysis of NAMD and GROMACS molecular dy-namics packages has been done.The benchmarks of 72 and 128 Dipalmitoylphos-phatidylcholine(DPPC)/water have been constructed using a cluster(3GHz-Xeon p...The comparable feature analysis of NAMD and GROMACS molecular dy-namics packages has been done.The benchmarks of 72 and 128 Dipalmitoylphos-phatidylcholine(DPPC)/water have been constructed using a cluster(3GHz-Xeon proces-sors and Myrinet network)and the comparison has been performed using GROMOS87 and CHARMM27 force fields modified for lipids with GROMACS and NAMD software packages,respectively.The GROMACS has been displayed as faster than NAMD,likely due to united-atom character of GROMACS and good implementation features.The GROMACS reaches saturation and goes to the worst results,the reason of which is that the program spends more time on communications between processors.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
Macular neovascularization(MNV)is the hallmark of neovascular age-related macular degeneration(nAMD),one of the leading causes of vision loss in the developed world.The current MNV standard of care including frequent ...Macular neovascularization(MNV)is the hallmark of neovascular age-related macular degeneration(nAMD),one of the leading causes of vision loss in the developed world.The current MNV standard of care including frequent intravitreal anti-vascular endothelial growth factor(VEGF)injections,although has revolutionized favorably the treatment,places a substantial burden on patients,caregivers,and physicians.Brolucizumab is a newly developed single-chain antibody fragment that inhibits activation of VEGF receptor 2 with in vitro affinity and potency comparable to commercially-available anti-VEGF agents.Its small molecular weight and its design allow for high solubility and retinal tissue penetration,and improve binding affinity to the target.Also a high clearance rate leading to minimal systemic exposure was observed.Brolucizumab has shown similar gains in visual acuity compared with other anti-VEGF molecules but a higher and earlier resolution of nAMD related fluid,achieving sustained macular dryness with longer mantainance injection interval ranging from 8 to 12 weeks after monthly loading doses.Rare cases of ocular inflammation also including retinal vasculitis and retinal vascular occlusions referred to an immune-mediated reaction posed safety concerns on selected patients and mantainance treatment interval shorter than 8 weeks.The present review summarizes several key points including the molecular structure and pharmacokinetics,the preclinical and clinical evidence of brolucizumab administration evaluating its efficacy,tolerability,and safety,extended dosing regimens and other indications still under clinical investigation.展开更多
文摘NAMD是美国伊利诺伊大学厄本纳-香槟分校(University of Illinois at Urbana-Champaign,UIUC)开发的著名大规模分子动力学并行计算软件包,NAMD是当前用来在分子水平上进行生命过程模拟研究的主要软件之一。我们在中国科学院计算机网络信息中心的"深腾7000"百万亿次超级计算机上进行了移植和优化,并对STMV典型的烟草花叶卫星病毒进行了2048处理器核的模拟计算,计算测试表明取得了较好的加速效果。
文摘The parallel scaling (parallel performance up to 48 cores) of NAMD package has been investigated by estimation of the sensitivity of interconnection on speedup and benchmark results—testing the parallel performance of Myrinet, Infiniband and Gigabit Ethernet networks. The system of ApoA1 of 92 K atoms, as well as 1000 K, 330 K, 210 K, 110 K, 54 K, 27 K and 16 K has been used as testing systems. The Armenian grid infrastructure (ArmGrid) has been used as a main platform for series of benchmarks. According to the results, due to the high performance of Myrinet and Infiniband networks, the ArmCluster system and the cluster located in the Yerevan State University show reasonable values, meanwhile the scaling of clusters with various types of Gigabit Ethernet interconnections breaks down when interconnection is activated. However, the clusters equipped by Gigabit Ethernet network are sensitive to change of system, particularly for 1000 K systems no breakdown in scaling is observed. The infiniband supports in comparison with Myrinet, make it possible to receive almost ideally results regardless of system size. In addition, a benchmarking formula is suggested, which provides the computational throughput depending on the number of processors. These results should be important, for instance, to choose most appropriate amount of processors for studied system.
基金the INTAS under YS Fellowship Ref.Number 03-55-699.
文摘The comparable feature analysis of NAMD and GROMACS molecular dy-namics packages has been done.The benchmarks of 72 and 128 Dipalmitoylphos-phatidylcholine(DPPC)/water have been constructed using a cluster(3GHz-Xeon proces-sors and Myrinet network)and the comparison has been performed using GROMOS87 and CHARMM27 force fields modified for lipids with GROMACS and NAMD software packages,respectively.The GROMACS has been displayed as faster than NAMD,likely due to united-atom character of GROMACS and good implementation features.The GROMACS reaches saturation and goes to the worst results,the reason of which is that the program spends more time on communications between processors.
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。
文摘Macular neovascularization(MNV)is the hallmark of neovascular age-related macular degeneration(nAMD),one of the leading causes of vision loss in the developed world.The current MNV standard of care including frequent intravitreal anti-vascular endothelial growth factor(VEGF)injections,although has revolutionized favorably the treatment,places a substantial burden on patients,caregivers,and physicians.Brolucizumab is a newly developed single-chain antibody fragment that inhibits activation of VEGF receptor 2 with in vitro affinity and potency comparable to commercially-available anti-VEGF agents.Its small molecular weight and its design allow for high solubility and retinal tissue penetration,and improve binding affinity to the target.Also a high clearance rate leading to minimal systemic exposure was observed.Brolucizumab has shown similar gains in visual acuity compared with other anti-VEGF molecules but a higher and earlier resolution of nAMD related fluid,achieving sustained macular dryness with longer mantainance injection interval ranging from 8 to 12 weeks after monthly loading doses.Rare cases of ocular inflammation also including retinal vasculitis and retinal vascular occlusions referred to an immune-mediated reaction posed safety concerns on selected patients and mantainance treatment interval shorter than 8 weeks.The present review summarizes several key points including the molecular structure and pharmacokinetics,the preclinical and clinical evidence of brolucizumab administration evaluating its efficacy,tolerability,and safety,extended dosing regimens and other indications still under clinical investigation.
