人类p53肿瘤蛋白的偏好性分析及其应用*

为了深入研究人类p53肿瘤蛋白,对七条最新的人类p53肿瘤蛋白的mRNA序列的偏好性及其同源性进行了分析。利用MEGA4.0（molecular evolutionary genetics analysis）软件的Distance功能得到七条基因的mRNA序列及其相应的蛋白质序列的同源性,并通过比较它们的RSCU和QRSCU值,对p53基因发生突变时偏好使用同义密码子的情况进行了分析。研究结果表明,基于拟氨基酸编码方法能更明显地展示出它们对同义密码子的一致偏好性,并且p53基因发生突变时偏好使用以c/g结     

ACOT1蛋白突变的分子动力学研究

酰基辅酶硫酯酶(Acyl-CoA thioesterases,ACOTs),也被称作酰基辅酶A水解酶,是一类能够水解酰基辅酶A酯类水解的酶,在脂肪酸的代谢中起着重要的作用。文中通过将序列分析得到的ACOT1的有害突变序列(ACOT1_MULT)和野生型序列利用同源建模的方法得到了相应的蛋白结构,并利用分子动力学模拟的方法研究了突变氨基酸对蛋白结构造成的影响。研究结果发现:突变蛋白在分子动力学过程中活性中心上面的"盖子"(LEU374-SER380)区域打开,而野生型一直处于关闭状态。通过对氢键和疏水作用的分析发现,突变位置的氨基酸(ALA189THR)与蛋白序列中的GLY169形成了新的氢键,突变残基附近的氢键也发生了很大的变化,导致了邮水解酶区域的第3个β折叠的末端Loop区(160Loop)朝着外侧的亲水性区域拉伸。160Loop区域的变化使得它与"盖子"区域之间的疏水相互作用消失,"盖子"区域的稳定性下降,并最终导致了"盖子"的打开。该结果对ACOT1蛋白相关的人类免疫病毒缺陷疾病和附睾炎等疾病的发病机理的研究具有很好的借鉴作用,同时也为基于该活性区域的抑制剂筛选工作提供了新的靶点。     

幽门螺杆菌TNF-α诱导蛋白的生物信息学分析

肿瘤坏死因子诱导蛋白Tipα是幽门螺杆菌特有的一个膜相关蛋白.它可以激活核因子κB,并诱导多种细胞因子和趋化因子的表达,导致胃炎和随后的肿瘤发生.它是幽门螺杆菌和胃癌发生之间的关键分子.本文利用生物信息学工具分析Tipα序列,预测其信号肽、跨膜区、疏水性、二级结构、三级结构等性质.结果:Tipα具有一段信号肽、脂蛋白信号肽酶切位点及脂盒模体.另外该蛋白没有跨膜区,可能是一个外周膜蛋白.Tipα的三级结构说明,该蛋白形成了一个致密的球状结构,Tipα的二级结构以α螺旋为主.     

苏云金杆菌Ⅲ型抗癌晶体蛋白的分子模建

通过同源建模获得抗癌晶体蛋白Parasporin-3的仞始三维结构,利用分子动力学方法优化之.分析模建分子的结构.最后利用Ramachandran plot,结构匹配等方法评价模型.结果显示Parasporin-3蛋白模型分子具有3个结构域,与经典的杀虫晶体蛋白结构相似,蛋白模型分子中的键长、键角以及二面角的分布合理,与模版蛋白的主链а碳原子的均方根差RMSD值为0.486751,在合理范围之内,表明Parasporin-3蛋白模型良好.并对Ⅲ型抗癌晶体蛋白的两种蛋白的预测结构进行了比较.为抗癌晶体蛋白的抗癌的分子机制及其定向改造提供信息.     

基于状态观测器的双馈风电机组变流器开关管开路故障检测

针对双馈风电机组变流器可靠性较差,一旦变流器开关管发生故障,整个风电机组可能遭到严重损坏甚至导致停机的问题,提出一种基于状态观测器的双馈风电机组转子侧变流器开关管开路故障检测方法.根据双馈风电机组拓扑结构,结合其感应电机和变流器进行整体建模;构建状态观测器以实现对转子侧电流的在线估计并生成残差;将残差与设定的阈值比较,判断是否有故障发生.仿真结果证明该方法可行且有效.     

基于DNA链置换技术的10线-4线优先编码器设计与实现

近年来,DNA链置换技术成为十分热门的技术领域,在众多的领域有广泛的应用,如DNA链置换技术被用于构造DNA纳米结构和逻辑计算系统等.DNA链置换技术与荧光标记技术的结合,使得DNA逻辑电路系统的思想成为现实.本文提出了一种基于DNA链置换技术的10线-4线邮箱编码器,其中使用了Seesaw模块作为基本单元.本文使用VisualDSD软件对所设计的电路系统进行了仿真模拟,结果显示:模型结构稳定,能够稳定高效实现10线-4线优先编码器的功能.     

基于QRSCU方法的RHD基因的偏好性研究及其应用

Rh血型系统作为人类最复杂的血型系统之一,其临床意义仅次于ABO血型系统.研究人类Rh血型系统中RHD基因对同义密码子的使用偏好性有助于从生物信息学角度了解RHD基因的编码特征.本文基于拟氨基酸编码方法,计算了人类Rh血型系统中RHD基因的同义密码子的相对使用度(quasi relative synonymous codonusage,QRSCU)及4种碱基分别出现在密码子3'端的相对频率(quasi relative frequency of nucleotide to codon3',QRFN3').通过分析计算结果中RHD基因的QRSCU值,得出RHD基因偏好使用以C或G结尾的同义密码子,也说明RHD基因偏好使用密码子-反密码子结合作用强的同义密码子,且避免使用结合作用中度的同义密码子.另外,通过分析计算结果中RHD基因的ORFN3'值,得出RHD基因的同义密码子对后面所接的第一个碱基的使用也有很强的使用偏好性.     

抑癌基因p53密码子偏好性分析及其突变致癌预测

p53是人类恶性肿瘤中最常见的突变基因,与人类肿瘤的发生相关性最高,也是基因研究中热度最高的基因之一。为深入研究人类p53基因突变机理,选取了6条人类p53基因mRNA序列。首先,利用基于RSCU方法下的多重变量分析软件CodonW对影响密码子使用的各项参数进行计算和统计分析,分析可得,密码子适应指数(CAI)与最优密码子使用频率(FOP)、密码子偏爱指数(CBI)均呈极显著正相关(p<0.01);有效密码子数(ENC)与密码子偏爱指数(CBI)、GC含量、GC3s、最优密码子使用频率(FOP)、第三位碱基G3s、密码子适应指数(CAI)均呈极显著负相关(p<0.01)。然后,再利用QRSCU编码方法,对p53密码子偏好性间距进行了分析设计,得出了基于拟氨基酸编码的方法能充分体现p53密码子对同义密码子的一致偏好性的结论,且p53基因更偏好使用以c或g结尾的同义密码子。以上各项参数也充分验证了拟氨基酸编码方法与p53密码子偏好性研究结果的紧密关联性。最后,结合前人对抑癌基因p53突变致癌的研究,对该6条基因序列作了病变预测,从而为人类恶性肿瘤的预防和预测提供重要的理论依据。     

一种基于HMM的蛋白质侧链旋转异构体构造方法

蛋白质侧链预测是蛋白质结构预测以及蛋白质设计中非常重要的子问题,而旋转异构体库的构造是进行侧链预测的基础,为预测提供搜索空间.现有的旋转异构体库考虑的是单个氨基酸的统计信息,没有考虑与之相邻的氨基酸对其构象产生的影响.本文提出一种基于隐马尔科夫模型的旋转异构体库构造方法,将相邻氨基酸的构象信息也考虑进来,产生与序列相关的旋转异构体库.并采用蛋白质预测程序Rosetta对CASP8中的12个自由建模蛋白质在本文提出的旋转异构体库基础上进行侧链预测,与基于经典的旋转异构体库的侧链预测结果相比,在预测精度上有了一定的提高.     

HClO对贻贝粘附单元DOPA氧化的理论研究

采用量子化学密度泛函理论(DFT)研究贻贝粘附单元DOPA(3,4-二羟基苯丙氨酸)的结构与性质,得分子的几何构型、原子电荷分布、反应活性及热力学等参数,表明:DOPA苯环易与HClO(次氯酸)发生亲电取代反应(1),生成3-氯4,5-二羟基苯丙氨酸,阻碍生成贻贝内超强粘附单元DOPA二联体,降低粘附蛋白间粘性;DOPA侧链易与HClO发生亲电亲核反应(2),促使DOPA侧链的断裂,降低粘附蛋白内粘性;在相同温度下,反应(1)和反应(2)的△G<0,且△G(1)<△G(2),反应(1)较易发生.     

Structural-symmetry-related sequence patterns of the proteins of beta-propeller family

It is still not very clear to what extent and how does the amino acid sequences of proteins determine their tertiary structures. In this paper, we report our investigations of the sequence-structure relations of the proteins in the beta-propeller fold family, which adopt highly symmetrical tertiary structures while their sequences appear "random". We analyzed the amino acid sequences by using a similarity matrix plus Pearson correlation method and found that the sequences can show the same symmetries as their tertiary structures only if we deduce the conditions of sequence similarity. This suggests that some key residues may play an important role in the formation of the tertiary structures of these proteins.     

Sarbanes—Oxley and Enterprise Security: IT Governance — What It Takes to Get the Job Done

Abstract

Several sections of the Sarbanes— Oxley Act of 2002 (SOX) directly affect the governance of the information technology (IT) organization, including potential SOX certification by the chief information officer, Section 404 internal control assessments, “rapid and current” disclosures to the public of material changes, and authentic and immutable record retention. The Securities and Exchange Commission (SEC) requires publicly traded companies to comply with the Treadway Commission's Committee of Sponsoring Organizations (COSO) that defines enterprise risk and places security as a critical variable in enterprise risk assessment. Effective IT and security governance are examined in terms of SOX compliance. Motorola IT security governance demonstrates effective structures, processes, and communications; centralized security leaders participate with Motorola's Management Board to create an enabling security organization to sustain long-term change.     

Computational prediction of the three-dimensional structures for the Caenorhabditis elegans tubulin family

In this article we characterize, from a structural point of view, all 16 members of the tubulin gene family of Caenorhabditis elegans (9 alpha-tubulins, 6 beta-tubulins, and 1 gamma-tubulin). We obtained their tertiary structures by computationally modifying the X-ray crystal structure of the pig brain alpha/beta-tubulin dimer published by Nogales et al. [Nature (London) 1998;391:199-203]. Our computational protocol involves changing the amino acids (with MIDAS; Jarvis et al., UCSF MIDAS. University of California, San Francisco, 1986) in the 3D structure of pig brain alpha/beta-tubulin dimer followed by geometry optimization with the AMBER force field (Perlman et al., AMBER 4. University of California, San Francisco, 1990). We subsequently analyze and compare the resulting structures in terms of the differences in their secondary and tertiary structures. In addition, we compare the pattern of hydrogen bonds and hydrophobic contacts in the guanosine triphosphate (GTP)-binding site for all members of the tubulin family. Our computational results show that, except for gamma-tubulin, all members of the C. elegans tubulin family have similar secondary and 3D structures and that the change in the pattern of hydrogen bonds in the GTP-binding site may be used to assess the relative stability of different alpha/beta-tubulin dimers formed by monomers of the tubulin family.     

应用计算机对比分析苏云金杆菌Cry1A类晶体蛋白

蛋白质的结构数据量目前还远落后于其序列数据量。本文利用蛋白质数据库和CLUSTAL W、SWISS-MODEL、ExPASy工具等对已知序列的9种Cry1A的一级结构及基本性质、二级结构、三级结构进行预测分析对比,发现其序列和结构的均高度相似,从而找出序列上的主要突变区域和三维结构的差异部位,有助于进一步认识Cry1A蛋白的作用模式和功能异同、分析其进化关系,并为重新设计Cry1A蛋白提供参考。     

Sox Compliance with OEE,Enterprise Modeling and Temporal-ABC

The Sarbanes-Oxley (SOX) Act 2002 resulted from the mounting accounting and corporate scandals in the late 1990s and early 2000s. Since the passage of the SOX Act, companies are facing even greater challenges to meet raised expectations to provide accurate, visible, and timely information for SOX compliance. This research puts forth a systems design framework to achieve a real time, accurate, consistently traceable and easily verifiable SOX compliant technology. Our multidisciplinary and integrative systems design incorporates Overall Equipment Effectiveness (OEE) to ensure effective business performance within a knowledge represented company modeled as Enveloped Activity Based Enterprise Model (EABEM) that facilitates Temporal-Activity Based Costing (ABC) so as to effectively lead to accurate, traceable and verifiable operational cost transparencies necessary for SOX compliance.     

On the structure, interactions, and dynamics of bound VEGF

The vascular endothelial growth factor (VEGF) is believed to be the most important protein in the regulation of the angiogenic cascade. Thus, exploring the structure and dynamical properties of this growth factor and the influence of receptor and inhibitor binding to these properties may reveal new insights on VEGF's biological process and inhibition opportunities. Here we describe an analysis of molecular dynamics simulations of VEGF bound to the Flt-1 receptor, VEGF bound to the v107 peptide inhibitor, and also VEGF bound to a mutant v107. We analyze the effects of binding to VEGF regarding three aspects: structure, interactions, and dynamics. We found that the structure of VEGF is not significantly perturbed upon binding. We analyze the individual contribution of the VEGF residues to the total interaction energy of binding to Flt-1 and v107. We also compare dynamical variables such as thermal fluctuations and correlations with those of the unbound form. We found that receptor binding is able to promote stronger perturbations on the VEGF dynamical behavior than VEGF inhibitor binding. VEGF motions in the receptor bound complex are shown to be less correlated than motions of unbound VEGF. The work addresses the changes on conformational flexibility of the isolated VEGF upon binding, as well as changes in structure and side-chain rearrangements.     

Checking semantic correctness of a class of structured programs by program function construction

A new approach to symbolic execution of structured FORTRAN programs is proposed. The properties of new elementary program structures are studied and symbolic execution of compositions of these structures are considered.Translated from Kibernetika i Sistemnyi Analiz, No. 5, pp. 107–110, September–October, 1991.     

Inter-ring rotation of apolipoprotein A-I protein monomers for the double-belt model using biased molecular dynamics

The double belt model for lipid-bound discoidal apolipoprotein A-I consists of two alpha-helical monomers bound about an unilamellar bilayer of lipids. Previous work, based on salt bridge calculations, has demonstrated that the L5/5 registration, Milano mutant, and Paris mutant are preferred conformations for apolipoprotein A-I. The salt bridge scoring indicated better energetic scoring in these alignments. The Paris (R151C) and Milano (R173C) mutants indicate a mode of change must be available. To find proper registration, one proposed change is a 'rotationally' independent circular motion of the two protein monomers about the lipid unilamellar bilayer core. Here, we present computational data for independent inter-ring rotation of the two alpha-helical monomers about the lipid unilamellar bilayer core. The simulations presented here support the existing double-belt model. We find the rotation of the two protein monomers is able to occur with biasing. We determine that a cysteine mutant at Glu107 as a possible target for future mutational studies. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling through dynamics has substantial biomedical implications.     

用AVHRR资料反演青藏高原东北部陆面温度和气温

利用1986年10月-1988年5月NOAA-9和NOAA-10两颗卫星的AVHRR通道1、2和4的资料和同期107个地面台站资料，建立由卫星资料反演地面温度和气温的二元、三元回归方程，并讨论了标准化植被指数NDVI在下垫面分区以及在反演陆面温度中的作用。     

Computational studies of the resistance patterns of mutant HIV-1 aspartic proteases towards ABT-538 (ritonavir) and design of new derivatives

Kinetic characterization and cross resistance pattern studies of HIV-1 aspartic protase (PR) inhibitors have shown that some mutations cause considerable reduction in inhibition efficiency. We have performed a computational study of the binding of ABT-538 (ritonavir) with wild type (wt) PR and 12 model mutant structures (R8Q, V321, M461, V82A, V82F, V821, I84V, M46I/V82F, M46I/I84V, V32I/I84V, V82F/I84V and V32I/K45I/F53L/A71V/I84V/L89M (6X)) for which inhibition data are available. Our computational studies indicate a significant correlation between computed complexation energies of ABT-538 with the modeled mutant enzyme structures and the corresponding experimental inhibition constants. By evaluating non-bonding interaction energies between the inhibitor and the mutant enzymes, we have carried out a mechanistic analysis to ascertain the reasons underlying the decrease in binding affinities. This analysis indicated that several residues in addition to the mutated residues contribute to the loss of binding. Taking these considerations into account, a number of new derivatives of ABT-538 were designed, so as to increase van der Waal's and hydrogen bonding interactions with selected mutants. A significant improvement in calculated complexation energies towards both mutant and wt PR structures was obtained for several of the redesigned analogues.