Modeling the intact form of the {alpha}1-proteinase inhibitor

The structure of the intact form of the serpin SRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">₁-proteinaseinhibitor has been modeled based on the assumption that thecentral strand s4A of the six-stranded ß-sheet A ofthe cleaved inhibitor is not incorporated into the sheet ofintact SRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">₁-proteinase inhibitor. This strand was removed fromits position in the center of the sheet by suitable rotationsabout the backbone dihedrals of Lys343 using molecular graphics.The resulting structure was then annealed using molecular dynamics(MD) while applying progressive distance restraints to the reactivepeptide bond (Met358-Ser359) for 50 ps. During this time, thedisrupted ß-sheet reformed to create a five-strandedß-sheet with strands 3 and 5 in a parallel arrangement.This change and accompanying structural rearrangements are largelyconfirmed by the X-ray structure of plakalbumin, whose structurereflects the overall structure of intact serpins. The successfulmodeling experiment demonstrates the utility of MD for makinggross structural predictions based on related structures. Thebinding loop of the intact form is modeled to allow dockingwith serine proteinases, in particular thrombin, which mosthighly constrains the possible conformations of the bindingloop.     

Replacing the ({beta}{alpha})-unit 8 of E.coli TIM with its chicken homologue leads to a stable and active hybrid enzyme

In order to investigate how structural modifications interferewith protein stability, we modified a (ßSRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">)-unit inE.coli triosephosphate isomerase (TIM), a typical (ßSRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">)-barrelprotein, assuming that the pseudosymmetrical ß-barrelcan be divided into eight successive loop/ß-strand/loop/SRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">-helixmotifs. We replaced the eighth (ßSRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">)-unit of E.coliTIM with the corresponding chicken (ßSRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">)-unit. The substitution,involving the replacement of 10 of the 23 residues of this (ßSRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">)-unit, was evaluated first by modelling, then experimentally.Modelling by bomology suggests how the amino add replacementsmight be accommodated in the hybrid E.coli/chicken TIM (ETCM8CHI).Both natural and hybrid recombinant TIMs, overproduced in E.coli,were purified to homogeneity and characterized as to their stabilityand kinetics. Our kinetic studies show that the modificationperformed here leads to an active enzyme. The stability studiesindicate that the stability of ETIM8CHI is comparable to thatof the wild type TIM.     

A sequence motif in the transmembrane region of growth factor receptors with tyrosine kinase activity mediates dimerization

A mechanism by which ligand binding to the extracellular domainof a growth factor receptor causes activation of its cytoplasmictyrosine kinase domain is that binding promotes receptor dimerization.Recently we proposed a model in which dimerization of the transmembraneSRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">-helices in one member of this family, rat neu, is mediatedby the presence of three specific residues. This paper showsthat a similar sequence motif is observed in 18 of the 20 transmembraneSRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">-helices of the tyrosine kinase family of growth factor receptors.The motif encompasses a five residue segment in which position0 (P0) requires a small side chain (Gly, Ala, Ser, Thr or Pro),P3 an aliphatic side chain (Ala, Val, Leu or Ile) and P4 onlythe smallest side chains (Gly or Ala). In addition other featuresof the transmembrane sequences are reported. It is concludedthat the dimerization of transmembrane SRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">-helices may be a generalmechanism of tyrosine kinase activation in this family of growthfactor receptors.     

A holistic approach to protein structure alignment

A method of protein structure comparison developed previouslyis extended to incorporate other aspects of protein structurein addition to the inter-atomic vectors on which it was originallybased. Each additional aspect, which included hydrogen bonding,solvent exposure, torsional angles and sequence, was introducedseparately and evaluated for its ability to improve alignmentquality. The components were then combined, suitably weighted,to produce a more holistic comparison method. The method wastested on a group of remotely related ß/SRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0"> type proteinsthat share a common feature in their overall chain fold. Theresults indicated that while the original inter-atomic vectorcomponent was sufficient to give the correct alignment of mostpairs of topologically equivalent proteins, the inclusion ofhydrogen bonds, torsion angles and a measure of solvent exposureled to improvements in the more difficult comparisons. Considerationof amino acid properties, including hydrophobicity, had no beneficialeffect. The failure of the latter component was not unexpectedconsidering the almost total lack of sequence similarity amongthe proteins considered.     

Molecular modelling of Staphylococcal {delta}-toxin ion channels by restrained molecular dynamics

SRC="http://peds.oxfordjournals.org/math/delta.gif" ALT="{delta}" BORDER="0">-Toxin is a 26-residue channel-forming peptide from Staphylococcusaureus which forms an amphipathic SRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">-helix in a membrane environment.Channel formation in planar bilayers suggests that an averageof six SRC="http://peds.oxfordjournals.org/math/delta.gif" ALT="{delta}" BORDER="0">-toxin helices self-assemble to form transbilayer pores.Molecular models for channels formed by SRC="http://peds.oxfordjournals.org/math/delta.gif" ALT="{delta}" BORDER="0">-toxin and by a syntheticanalogue have been generated using a simulated annealing protocolapplied via restrained molecular dynamics. These models areanalysed in terms of the predicted geometric and energetic propertiesof the transbilayer pores. Pore radius calculations of the modelsdemonstrate that rings of channel-lining residues contributea series of constrictions along the pore. Electrostatic propertiesof the pores are determined both by pore-lining charged sidechains and by the aligned helix dipoles of the parallel helixbundle. Molecular dynamics simulations (100 ps) of SRC="http://peds.oxfordjournals.org/math/delta.gif" ALT="{delta}" BORDER="0">-toxin modelscontaining intra-pore water were performed. Analysis of theresultant dynamics trajectories further supports the proposalthat alternative conformations of pore-constricting side chainsmay be responsible for the observed conductance heterogeneityof SRC="http://peds.oxfordjournals.org/math/delta.gif" ALT="{delta}" BORDER="0">-toxin ion channels.     

高含钢率SRC柱轴压承载性能研究

通过对3根含钢率为24.3%的SRC柱的轴压试验,对高含钢率SRC柱构件的轴压承载性能进行了研究。分析了试件的荷载-位移关系曲线特征,揭示了高含钢率SRC柱以钢骨为主要受力部分,依次发生混凝土开裂和压溃、钢筋屈曲、钢骨弯曲失稳等破坏形态。利用有限元软件ABAQUS对试验过程进行了模拟。研究表明,高含钢率SRC柱具有钢构件的承载特性,钢骨塑性阶段的整体失稳导致极限后的承载力下降;工程设计可以采用塑性准则和叠加原理计算其极限承载力。     

基于主动表观模型的稀疏聚类人脸识别算法

在复杂的非人脸成分干扰以及训练样本过大、训练样本之间相似度较高的条件下,原始稀疏表示分类(SRC)算法识别准确率较低。针对上述问题,提出一种基于主动表观模型的稀疏聚类(CS-AAM)人脸识别算法。首先,利用主动表观模型快速、准确地对人脸特征点进行定位,获取主要人脸信息;然后,对训练样本进行K-means聚类,将相似程度高的图像分为一类,计算聚类中心,将该中心作为原子构造过完备字典并进行稀疏分解;最后,计算稀疏系数和重构残差对人脸图像进行分类、识别。将该算法与最近邻(NN)、支持向量机(SVM)、稀疏表示分类(SRC)、协同表示分类(CRC)人脸识别算法在ORL和Extended Yale B人脸数据库上对不同样本数及不同维数的人脸图像分别进行识别率测试,在相同样本数或相同维数情况下CS-AAM算法识别率均高于其他算法。在ORL人脸库中选取样本数为210时,相同维数条件下CS-AAM算法识别率为95.2%;在Extended Yale B人脸库上选取样本数为600时,CS-AAM算法识别率为96.8%。实验结果表明,该算法能够有效地提高人脸图像的识别准确率。     

型钢混凝土空腹桁架连体结构研究应用--深圳大学科技楼连体结构解析

本文结合实际工程,对型钢混凝土空腹桁架连体结构进行了研究。通过三种连体结构动力性能的对比分析,验证了空腹桁架结构具有良好的抗震性能,有利于减缓连体结构引起的刚度突变、质量集中和支承结构的应力集中,有利于提高连体结构的延性。同时,本文研究了楼盖刚度和型钢混凝土长期刚度退化对连体结构受力变形的影响,提出了型钢混凝土空腹桁架这一新型桁架节点设计构造措施及控制施工工艺程序改善结构受力的措施。     

基于去调频宽带LFM信号的二次距离压缩算法及其实时实现

该文在基于匹配滤波的二次距离压缩算法(SRC)基础上,通过对去调频的线性调频(LFM)信号的时、频域关系的分析,给出基于去调频LFM信号的SRC算法,与距离多普勒算法(RD)和普通LFM信号SRC算法对比,分析该算法的运算量,说明该算法适合于去调频体制SAR实时成像处理。对于去调频SAR数据采用该算法压缩得到清晰的图像,同时对比斜视下SRC与RD成像的结果。验证了在高分辨率实时成像时SRC算法优于RD算法。     

Solution structure and dynamics of a serpin reactive site loop using interleukin 1 as a presentation scaffold

Human interleukin-1ß (IL1ß) was used as a presentationscaffold for the characterization of the reactive site loop(RSL) of the serpin SRC="http://peds.oxfordjournals.org/math/alpha.gif" ALT="{alpha}" BORDER="0">1-antitrypsin (A1AT), the physiologicalinhibitor of leukocyte elastase. A chimeric protein was generatedby replacement of residues 50–53 of IL1ß, correspondingto an exposed reverse turn in IL1ß, with the 10-residueP5-P5' sequence EAIPMSIPPE from A1AT. The chimera (antitrypsin-interleukin,AT-IL) inhibits elastase specifically and also binds the IL1ßreceptor. Multinuclear NMR characterization of AT-IL establishedthat, with the exception of the inserted sequence, the structureof the IL1ß scaffold is preserved in the chimera. Thestructure of the inserted RSL was analyzed relative to thatof the isolated 10-residue RSL peptide, which was shown to beessentially disordered in solution. The chimeric RSL was alsofound to be solvent exposed and conformationally mobile in comparisonwith the IL1ß scaffold, and there was no evidence of persistinginteractions with the scaffold outside of the N- and C-terminallinkages. However, AT-IL exhibits sigificant differences inchemical shift and NOE patterns relative to the isolated RSLthat are consistent with local features of non-random structure.The proximity of these features to the P1-P1' residues suggeststhat they may be responsible for the inhibitory activity ofthe chimera.