室温下的小蛋白折叠研究

目前,无论在实验还是理论研究方面,研究蛋白质的从头折叠即使是小蛋白的折叠也非常困难.在室温下研究蛋白质的折叠过程可以有效的阐述蛋白质折叠机制.笔者从2I9M的线性结构出发,在室温下运行了15 ns的分子动力学模拟,发现它在6.4 ns时成功折叠到了天然态结构,此时的结构与天然态结构的均方根偏差为1.17(A),模拟结构与天然态结构符合的非常好.折叠过程是首先在C端出现了螺旋,随后N端又出现了螺旋,然后螺旋从N端鱼贯式生成,最终形成天然态结构.     

GPU加速的并行模拟退火算法在蛋白质预测中的应用

人类基因组测序工作初步结果显示,MSAPSO算法在求解蛋白质折叠问题时具有不错的求解精度,但是算法执行的时间开销却令人难以接受.针对此问题,使用CUDA编程模型在GPU上实现MSAPSO算法(CUMSA),利用GPU的计算能力,节省求解问题的时间成本.实验结果显示,CUMSA对4条测试序列求解得到的解的质量相对较高,由得到的解的构象图可知,CUMSA能够高效、正确地进行蛋白质折叠结构预测.     

稻米中色氨酸的快速分析和江苏地区几种水稻良种色氨酸的比较

一、前言稻米为我国人民主要膳食,是蛋白质和热能的主要来源之一。众所周知,色氨酸(Tryptophan)(Trp)为人类及动物生长所必需,在营养上是一种必需氨基酸。在代谢上是5—羟色胺的前身,后者是一种能使血管收缩的物质,并且是一种有效的神经介质,起着镇定的药理作用。Trp在体内代谢其最终产物是烟酰胺,并以二核甘酸化合物形式存在,为NAD(辅酶I)与NADP(辅酶Ⅱ)的基本成份。同时Trp的代谢产物     

蛋白质折叠的计算机模拟

使用非格点朗之万模型和"Go型"氨基酸相互作用模拟了4个小分子量快速折叠蛋白质的折叠行为.从动力学和热力学两方面的探讨中,得到蛋白质CI2的折叠属于两态过程和蛋白质CheY的折叠过程存在中间态和蛋白质1BBL的折叠属于无势垒的"下山"式过程,而蛋白质片断1BDD(第10至第55残基)的折叠则是介于两态过程和"下山"式过程的中间类型.由于使用了相同的模型,物理机制上这些不同折叠类型显然来自蛋白质不同的天然态拓扑结构.     

ABEEMσπ/MM模型对蛋白质G_A88/G_B88水溶液动力学性质的研究

应用ABEEMσπ/MM（σπ水平的原子与键电负性均衡方法融合进分子力学）浮动电荷模型以及显性ABEEM-7P水模型,对GA88和GB88两个蛋白质分子进行了分子动力学模拟.分析了2个蛋白质的动力学性质,包括蛋白质的回旋半径、疏水表面积和亲水表面积、各类原子位置的均方根偏差以及氢键分布.通过对比水溶液和真空下2个蛋白质的回旋半径,表明该模型很好地体现了蛋白质的＂电致紧缩＂现象;对疏水表面积和亲水表面积的计算表明,GB88中残基与溶剂的相互作用更强一些;非氢原子位置的均方根偏差及氢键分布情况与实验结构相比较表明,ABEEMσπ/MM浮动电荷模型模拟的GA88和GB88的结构与实验结构有很好的一致性,进而说明该模型的合理性和参数的可转移性.     

不同城市冠层模式对城市地表能量平衡模拟能力的检验

城市地表能量平衡过程是城市大气边界层数值模式的关键过程之一,但对目前不同参数化的适用性和模拟性能评估工作较少.利用2013年南京市中心市区的湍流热通量的观测数据与单层冠层模式(Single Layer Urban Canopy Model,SLUCM)、局地气象参数化方案(Local-scale Urban Meteorological Parameterization Scheme,LUMPS)、城市能量和水平衡方案(Surface Urban Energy and Water Balance Scheme,SUEWS)以及公用陆面模式城市参数化方案(the Community Land Model Urban,CLMU)这四个模式的模拟结果进行对比分析.分析表明:(1)在能量平衡各项中,各模式对于净辐射的模拟颇好,其均方根误差普遍低于感热项的50%,潜热和储热项模拟较差.(2)各模式对净辐射均有低估,其中SLUCM模式模拟最佳,全年平均偏差约7.7%,其均方根误差10~20Wm-2左右;对于感热通量,SUEWS模式模拟较好,日间偏差低于7%;对于潜热通量,则是CLMU模式更佳,特别是夏秋冬三季,平均偏差约12.5%;对于储热项,SLUCM模拟较优,偏差低于10%,各季均方根误差也普遍低于其他模式的50%.(3)各模式普遍表现为:秋冬两季模拟优于春夏两季,夜间模拟比日间更佳.比较结果为数值模拟中城市冠层模式的选取与改进提供了参考依据.     

产生 N(0,1)随机变量的一个快速组合法

本文用密度分解法和查表法的结合构造出一个产生 N(0,1)随机变量的快速近似方法。在|x|>3区间上所生变量是概率精确的;在|x|≤3区间上,所生变量是概率近似的,其随机均方根偏差≤0.5×10~(-3),只在两端处的1%概率区间上,其随机均方根偏差≤0.34×10~(-2),此精度足以满足很大一类的实际问题的模拟.为了节省存贮,我们提出了一种“不等间距”的分割技巧,采用此技巧使存贮量以数量级下降,大大提高了查表法的实用价值.     

电荷与应变协同调控g-C9N7膜对CO2吸附和渗透特性的研究

为了有效捕获和分离CO₂，提出了一种电荷与应变协同调控的气体捕获和渗透的新方法，该方法具有可逆性和动力学可控的优点。采用分子动力学(MD)模拟和基于第一性原理密度泛函理论(DFT)计算，分析了不同电荷密度和拉伸应变控制下的多孔g-C₉N₇纳米片对CO₂捕获和渗透的影响规律。通过电荷调控策略，CO₂分子渗透率高达5.94×107 GPU(即0.019 899 mol/(s·Pa·m2))。另外，CO₂渗透率随拉伸应变率的增加而增大，拉伸应变率为7.5%的g-C₉N₇薄膜的最大渗透率为3.61×107 GPU(即0.012 094 mol/(s ·Pa ·m2))。在此基础上，采用负电荷与应变工程相结合的方法研究二者的协同效应，在负电荷为1 e、拉伸应变率为3.0%的条件下，CO₂渗透率达到3.18×107 GPU(即0.001 065 mol/(s ·Pa ·m2))。此时CO₂渗透率是仅施加1 e时CO₂渗透率的9倍，是仅添加3.0%应变率时CO₂渗透率的8倍。研究结果为开发具有CO₂捕获和分离高度可控的高性能材料提供了理论指导。     

一类拟线性退缩抛物方程

本文研究拟线性抛物方程(其中α(0)=α(M)=0,α(s)>0(0相似文献   

同源建模方法预测蛋白质突变结构的适用性分析

通过从Protein Data Bank(PDB)结构数据库中提取单氨基酸突变的晶体结构,构建了一组无冗余的测试数据集,对目前应用最广泛的两款同源建模预测软件(SWISS-MODEL和MODELLER)进行了测试分析,发现它们对蛋白质的整体结构预测效果良好,均方根偏差小于0.5埃(RMSD0.5),但在突变导致结构显著变化(RMSD1.5)的情况下却均不能得到准确结果.分类统计显示,发生在蛋白质结构内部和极性氨基酸之间的突变结构变化小,两款软件预测效果较好(RMSD1.0).突变导致结构显著变化的可能性不高(5%),但它对蛋白质功能的影响不可忽视,因此应用同源建模方法对于蛋白质突变的模拟并不完全适用,还需要开发新方法来提高准确性.     

氰戊菊酯对Tn细胞系P450及蛋白质谱表达的影响

研究氰戊菊酯对粉蚊夜蛾(Trichoplusia ni, Tn)细胞系细胞色素P450(P450s)的诱导作用及蛋白质谱表达的影响.用MTT法和台盼兰法观察不同浓度氰戊菊酯处理Tn细胞12 h后细胞的存活率;光谱测定法测定P450s含量;以12.5 μmol/L氰戊菊酯处理Tn细胞12 h,通过二维液相色谱分离技术分析处理前后Tn细胞系蛋白质谱的变化.结果显示：当氰戊菊酯处理浓度高于17.5 μmol/L时,Tn细胞形态发生明显变化,且细胞死亡率显著高于对照组(P<0.01).P450s的含量有随氰戊菊酯浓度增加而升高的趋势,并在氰戊菊酯浓度为12.5 μmol/L时达到最高(8.562 nmol/mg protein);P450s的含量亦有随处理时间延长而升高的趋势,且在12 h时达到最高(5.28±1.14 nmol/mg protein).通过二维液相色谱分离技术得到124个差异组分,其中42个组分上调,82个组分下调.结果表明：氰戊菊酯对P450s确有诱导作用,且氰戊菊酯诱导前后Tn细胞中蛋白的变化可能与P450s诱导途径中某些受体的变化有关.     

Multiple Suppressive Effects of a Protein from Caesalpinia minax on Murine Melanoma Cells

IntroductionIn recent years,a great deal of attention hasfocused on finding potential anti- tumor agentsfrom natural sources[14 ] .A vast number ofpromising candidate molecules,especiallycomponents extracted from plants,have beenevaluated[59] .　 Herbs have a long history of use as Chinesetraditional medicine.Caesalpinia minax (C.minax) is a wild plantin Yunnan Province,China.The high level of ultraviolet radiation in thistropical province causes widespread skin diseases inthis area.Extract…     

(6,5)笼图(n,5)笼(n≤7)的统一

本文给出了(6,5)笼图,并且对它的正确性进行了间接地论证,同时又以同样的思想和方法给出了(5,5)笼,(7,5)笼的同构图,此时又意外地得到了(4,5)笼,于是,(3,5)笼,(4,5)笼,(5,5)笼,(6,5)笼,(7,5)笼便得到了完美地统一。     

Structural basis for the function and inhibition of an influenza virus proton channel

The M2 protein from influenza A virus is a pH-activated proton channel that mediates acidification of the interior of viral particles entrapped in endosomes. M2 is the target of the anti-influenza drugs amantadine and rimantadine; recently, resistance to these drugs in humans, birds and pigs has reached more than 90% (ref. 1). Here we describe the crystal structure of the transmembrane-spanning region of the homotetrameric protein in the presence and absence of the channel-blocking drug amantadine. pH-dependent structural changes occur near a set of conserved His and Trp residues that are involved in proton gating. The drug-binding site is lined by residues that are mutated in amantadine-resistant viruses. Binding of amantadine physically occludes the pore, and might also perturb the pK(a) of the critical His residue. The structure provides a starting point for solving the problem of resistance to M2-channel blockers.     

拟南芥对镉胁迫的生理响应

研究拟南芥对不同Cd2+浓度处理（0、20、40、60和80 μM）的生理响应，以探讨Cd2+对植物的毒性效应及植物的耐性机理.结果发现，各浓度Cd2+导致拟南芥过氧化氢酶和超氧化物歧化酶活性显著降低（P<0.05）、植物根部细胞DNA出现明显的损伤，拟南芥生物量及根长也显著降低（P<0.05），表明Cd2+对拟南芥体内的生物大分子产生了严重的胁迫效应.叶片光合色素含量随Cd2+浓度的升高而逐渐下降，在60和80 μM时处理效应达到显著水平（P<0.05），表明高Cd2+抑制植物的光合作用.拟南芥体内丙二醛及可溶性蛋白含量随Cd2+浓度的增加明显上升，在60 μM时处理效应显著（P<0.05），表明Cd2+胁迫导致其膜脂过氧化效应.在全部Cd2+处理下，拟南芥体内谷胱甘肽和植物螯合肽的含量均显著上升（P<0.01）；类黄酮、花色素苷等酚类物质也随Cd2+浓度的增加而上升，并在高Cd2+浓度（60和80 μM）下处理效应达到显著水平（P<0.05），表明拟南芥通过积累具有活性氧抗性的次级代谢产物提高其对Cd2+的耐受性.本研究的结果能够为深入研究Cd2+对植物毒害的分子机制以及植物对Cd2+耐性的分子机制提供实验依据.     

Folding at the speed limit

Many small proteins seem to fold by a simple process explicable by conventional chemical kinetics and transition-state theory. This assumes an instant equilibrium between reactants and a high-energy activated state. In reality, equilibration occurs on timescales dependent on the molecules involved, below which such analyses break down. The molecular timescale, normally too short to be seen in experiments, can be of a significant length for proteins. To probe it directly, we studied very rapidly folding mutants of the five-helix bundle protein lambda(6-85), whose activated state is significantly populated during folding. A time-dependent rate coefficient below 2 micro s signals the onset of the molecular timescale, and hence the ultimate speed limit for folding. A simple model shows that the molecular timescale represents the natural pre-factor for transition state models of folding.     

彩虹表密码分析算法的图形处理器优化设计与实现

设计了一种在图形处理器(GPU)上的彩虹表密钥分析算法.结合GPU单指令多线程的特点改进了Oechslin的彩虹表算法,将预处理中彩虹链的计算分别映射到GPU的单个线程,并利用预计算链提高了在线分析的效率.所使用的硬件平台GPU Tesla C1060 相对于CPU Core2 Duo 2.8 GHz,在运行速度方面,预处理提高了41.2倍(每秒110×106次DES加密),在线分析提高了3.52倍.在此系统上用1.3 GB的磁盘空间,平均2.73 s的在线分析时间以及46%的概率,成功获得了加密选择明文的40 bit DES密钥.     

Atom-by-atom analysis of global downhill protein folding

Protein folding is an inherently complex process involving coordination of the intricate networks of weak interactions that stabilize native three-dimensional structures. In the conventional paradigm, simple protein structures are assumed to fold in an all-or-none process that is inaccessible to experiment. Existing experimental methods therefore probe folding mechanisms indirectly. A widely used approach interprets changes in protein stability and/or folding kinetics, induced by engineered mutations, in terms of the structure of the native protein. In addition to limitations in connecting energetics with structure, mutational methods have significant experimental uncertainties and are unable to map complex networks of interactions. In contrast, analytical theory predicts small barriers to folding and the possibility of downhill folding. These theoretical predictions have been confirmed experimentally in recent years, including the observation of global downhill folding. However, a key remaining question is whether downhill folding can indeed lead to the high-resolution analysis of protein folding processes. Here we show, with the use of nuclear magnetic resonance (NMR), that the downhill protein BBL from Escherichia coli unfolds atom by atom starting from a defined three-dimensional structure. Thermal unfolding data on 158 backbone and side-chain protons out of a total of 204 provide a detailed view of the structural events during folding. This view confirms the statistical nature of folding, and exposes the interplay between hydrogen bonding, hydrophobic forces, backbone conformation and side-chain entropy. From the data we also obtain a map of the interaction network in this protein, which reveals the source of folding cooperativity. Our approach can be extended to other proteins with marginal barriers (less than 3RT), providing a new tool for the study of protein folding.     

Fast Parallel Cutoff Pair Interactions for Molecular Dynamics on Heterogeneous Systems

Heterogeneous systems with both Central Processing Units (CPUs) and Graphics Processing Units (GPUs) are frequently used to accelerate short-ranged Molecular Dynamics (MD) simulations. The most time-consuming task in short-ranged MD simulations is the computation of particle-to-particle interactions. Beyond a certain distance, these interactions decrease to zero. To minimize the operations to investigate distance, previous works have tiled interactions by employing the spatial attribute, which increases the memory access and GPU computations, hence decreasing performance. Other studies ignore the spatial attribute and construct an all-versus-all interaction matrix, which has poor scalability. This paper presents an improved algorithm. The algorithm first bins particles into voxels according to the spatial attributes, and then tiles the all-versus-all matrix into voxel-versus-voxel sub-matrixes. Only the sub-matrixes between neighboring voxels are computed on the GPU. Therefore, the algorithm reduces the distance examine operations and limits additional memory access and GPU computations. This paper also adopts a multi-level programming model to implement the algorithm on multi-nodes of Tianhe-lA. By employing (1) a patch design to exploit parallelism across the simulation domain, (2) a communication overlapping method to overlap the communications between CPUs and GPUs, and (3) a dynamic workload balancing method to adjust the workloads among compute nodes, the implementation achieves a speedup of 4.16x on one NVIDIA Tesla M2050 GPU compared to a 2.93 GHz six-core Intel Xeon X5670 CPU. In addition, it runs 2.41x faster on 256 compute nodes of Tianhe-lA (with two CPUs and one GPU inside a node) than on 256 GPU-excluded nodes.     

蛇菰内生菌Aspergillus sp. SHG-7 代谢产物研究

从药用植物宜昌蛇菰(Balanophora henryi Hesml.)中分离得到一株内生真菌Aspergillus sp. SHG-7,通过固体发酵,乙酸乙酯萃取得浸膏,其浸膏经硅胶柱层析、Sephadex LH-20、半制备型HPLC等分离手段分离得到6个化合物,经核磁共振、质谱等手段鉴定其结构分别为灰黄霉素(1),麦角甾醇(2),麦角甾-7, 22-二烯-3, 6-二酮(3),麦角甾-7, 22-二烯-3, 5, 6-三醇(4),软脂酸-1-甘油酯(5),肉豆蔻酸(6).化合物1对MCF-7、A549及Hela细胞具有一定的细胞毒活性,IC50分别为18.36 ± 2.32 μM、26.58 ± 1.62 μM 和74.29 ± 1.34 μM,化合物2～化合物6对以上肿瘤细胞无明显活性.