基于蛋白质-DNA复合物晶体结构的DNA结构动力学特性研究

依据最新NDB数据库中蛋白质-DNA复合物晶体结构数据,考虑DNA结构的序列依赖特性,对10个二联体和36个约化的四联体计算了DNA动力学结构模型中的关键参数——力常数矩阵,矩阵中的非对角项反映了结构参数间的关联。利用改进的DNA结构动力学模型,可以方便地计算给定序列的结构动力学特性。     

融合标签技术在膜蛋白结构研究中的应用

膜蛋白高级结构的研究包括不同的层次,即膜蛋白拓扑学结构的研究、利用核磁共振技术和蛋白质晶体衍射技术对三维结构的研究,以及膜蛋白复合体的研究。在研究过程中,如果能够基于膜蛋白的拓扑学结构预测,选择合适的蛋白质或多肽融合标签,利用基因融合技术在基因水平上对膜蛋白进行改造,可以产生含有融合标签的重组膜蛋自,不仅具有原有膜蛋白的功能活性,还具有融合标签所特有的生理生化特性,将会极大地促进膜蛋白结构和功能的研究。我们就目前膜蛋白结构研究中所涉及的融合标签技术及其应用策略和所取得的进展做一简述。     

The dependence of all-atom statistical potentials on structural training database

An accurate statistical energy function that is suitable for the prediction of protein structures of all classes should be independent of the structural database used for energy extraction. Here, two high-resolution, low-sequence-identity structural databases of 333 alpha-proteins and 271 beta-proteins were built for examining the database dependence of three all-atom statistical energy functions. They are RAPDF (residue-specific all-atom conditional probability discriminatory function), atomic KBP (atomic knowledge-based potential), and DFIRE (statistical potential based on distance-scaled finite ideal-gas reference state). These energy functions differ in the reference states used for energy derivation. The energy functions extracted from the different structural databases are used to select native structures from multiple decoys of 64 alpha-proteins and 28 beta-proteins. The performance in native structure selections indicates that the DFIRE-based energy function is mostly independent of the structural database whereas RAPDF and KBP have a significant dependence. The construction of two additional structural databases of alpha/beta and alpha + beta-proteins further confirmed the weak dependence of DFIRE on the structural databases of various structural classes. The possible source for the difference between the three all-atom statistical energy functions is that the physical reference state of ideal gas used in the DFIRE-based energy function is least dependent on the structural database.     

Effects of electrical and structural remodeling on atrial fibrillation maintenance: a simulation study

Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably: in patients with long-term atrial fibrillation, fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls. This is due to electrical, structural, and contractile remodeling processes. We investigated mechanisms of how electrical and structural remodeling contribute to perpetuation of simulated atrial fibrillation, using a mathematical model of the human atrial action potential incorporated into an anatomically realistic three-dimensional structural model of the human atria. Electrical and structural remodeling both shortened the atrial wavelength--electrical remodeling primarily through a decrease in action potential duration, while structural remodeling primarily slowed conduction. The decrease in wavelength correlates with an increase in the average duration of atrial fibrillation/flutter episodes. The dependence of reentry duration on wavelength was the same for electrical vs. structural remodeling. However, the dynamics during atrial reentry varied between electrical, structural, and combined electrical and structural remodeling in several ways, including: (i) with structural remodeling there were more occurrences of fragmented wavefronts and hence more filaments than during electrical remodeling; (ii) dominant waves anchored around different anatomical obstacles in electrical vs. structural remodeling; (iii) dominant waves were often not anchored in combined electrical and structural remodeling. We conclude that, in simulated atrial fibrillation, the wavelength dependence of reentry duration is similar for electrical and structural remodeling, despite major differences in overall dynamics, including maximal number of filaments, wave fragmentation, restitution properties, and whether dominant waves are anchored to anatomical obstacles or spiralling freely.     

Mechanism of the enzymatic hydrolysis of cellulose: Effects of major structural features of cellulose on enzymatic hydrolysis

The susceptibility of cellulose to enzymatic hydrolysis is affected by the structural features of cellulosic materials. It has been suggested that the crystallinity and surface area of cellulose fibers are the most important structural features in this regard. This study investigated in depth the relative effects of these two structural features upon the enzymatic hydrolysis of cellulose and the change of the structural parameters of cellulose during the course of hydrolysis. It was found that the hydrolysis rate is mainly dependent upon the fine structural order of cellulose which can best be represented by the crystallinity rather than the simple surface area. Monitoring the changes in the structural parameters during the course of reaction showed that surface area is not a major limiting factor that slows hydrolysis in its late stages as has been suggested. This information concerning structural features is used to elucidate the mode of action of cellulase.     

Lightweight Design of Mechanical Structures based on Structural Bionic Methodology

With increasing concern over the excessive energy consumption and environment pollution, structural bionics is a viable new tool of lightweight design by mechanical engineers. The structural solutions derived from nature can be successfully transferred into technical construction for maximum structural efficiency from minimal resources. The goal of the study is to develop a standard methodology for bionic mechanical structures with dead-load reduction and performance improvement. Similarity theory and fuzzy assessment method are deployed for selection of analogical samples and analysis based on structure, loading and function similarities. The type spectrum of lightweight design is established for selection convenience and principle extraction, vital to concept designs. Finite element method is used as an effective tool for mechanical performance simulation and comparison. The rapid prototyping, investment casting and Numerical Control (NC) machining are discussed for model fabrication. The static and dynamic test results indicate that the bionic models are lighter but stiffer than the original ones. So by mimicking biological structural principles, the structural bionic design offers a new solution for updating traditional design concepts and achieving maximum structural efficiency.     

Conformational transitions of the three recombinant domains of human serum albumin depending on pH

Human serum albumin (HSA) is a protein of 66.5 kDa that is composed of three homologous domains, each of which displays specific structural and functional characteristics. HSA is known to undergo different pH-dependent structural transitions, the N-F and F-E transitions in the acid pH region and the N-B transition at slightly alkaline pH. In order to elucidate the structural behavior of the recombinant HSA domains as stand-alone proteins and to investigate the molecular and structural origins of the pH-induced conformational changes of the intact molecule, we have employed fluorescence and circular dichroic methods. Here we provide evidence that the loosening of the HSA structure in the N-F transition takes place primarily in HSA-DOM III and that HSA-DOM I undergoes a structural rearrangement with only minor changes in secondary structure, whereas HSA-DOM II transforms to a molten globule-like state as the pH is reduced. In the pH region of the N-B transition of HSA, HSA-DOM I and HSA-DOM II experience a tertiary structural isomerization, whereas with HSA-DOM III no alterations in tertiary structure are observed, as judged from near-UV CD and fluorescence measurements.     

Systematically assessing the influence of 3-dimensional structural context on the molecular evolution of mammalian proteomes

The 3-dimensional (3D) structural context of amino acid residues in a protein could significantly impact the level of selective constraint on the residues. Here, by analyzing 767 mammalian proteins, we systematically investigate how various 3D structural contexts influence selective constraint. The structural contexts we examined include solvent accessibility, secondary structure, and intramolecular residue-residue interactions. Through this analysis, we offer quantitative information on how 3D structural contexts affect the level of selective constraint.     

The effect of pH on the conformation and stability of the structure of plant toxin-ricin

The effect of pH on the conformation of ricin and its A- and B-chains has been studied by measuring their intrinsic fluorescence. At pH 5.0 and 7.5, the structural stability of toxin and subunits was estimated according to the denaturing action of guanidine hydrochloride. It was demonstrated that the fluorescence of native toxin and catalytic A-subunit does not depend significantly on pH in the range pH 3-8, whereas ricin B-chain undergoes a structural transition at pH less than 5.0. The structural stability of ricin and isolated chains differs significantly at pH 7.5 and 5.0; the structural stability of ricin and the A-chain increases, whereas that of the B-chain decreases.     

Structural analysis based on state-space modeling.

A new method has been developed to compute the probability that each amino acid in a protein sequence is in a particular secondary structural element. Each of these probabilities is computed using the entire sequence and a set of predefined structural class models. This set of structural classes is patterned after Jane Richardson''s taxonomy for the domains of globular proteins. For each structural class considered, a mathematical model is constructed to represent constraints on the pattern of secondary structural elements characteristic of that class. These are stochastic models having discrete state spaces (referred to as hidden Markov models by researchers in signal processing and automatic speech recognition). Each model is a mathematical generator of amino acid sequences; the sequence under consideration is modeled as having been generated by one model in the set of candidates. The probability that each model generated the given sequence is computed using a filtering algorithm. The protein is then classified as belonging to the structural class having the most probable model. The secondary structure of the sequence is then analyzed using a "smoothing" algorithm that is optimal for that structural class model. For each residue position in the sequence, the smoother computes the probability that the residue is contained within each of the defined secondary structural elements of the model. This method has two important advantages: (1) the probability of each residue being in each of the modeled secondary structural elements is computed using the totality of the amino acid sequence, and (2) these probabilities are consistent with prior knowledge of realizable domain folds as encoded in each model. As an example of the method''s utility, we present its application to flavodoxin, a prototypical alpha/beta protein having a central beta-sheet, and to thioredoxin, which belongs to a similar structural class but shares no significant sequence similarity.     

Structural effects of an LQT-3 mutation on heart Na+ channel gating

Computational methods that predict three-dimensional structures from amino acid sequences have become increasingly accurate and have provided insights into structure-function relationships for proteins in the absence of structural data. However, the accuracy of computational structural models requires experimental approaches for validation. Here we report direct testing of the predictions of a previously reported structural model of the C-terminus of the human heart Na(+) channel. We focused on understanding the structural basis for the unique effects of an inherited C-terminal mutation (Y1795C), associated with long QT syndrome variant 3 (LQT-3), that has pronounced effects on Na(+) channel inactivation. Here we provide evidence that this mutation, in which a cysteine replaces a tyrosine at position 1795 (Y1795C), enables the formation of disulfide bonds with a partner cysteine in the channel. Using the predictions of the model, we identify the cysteine and show that three-dimensional information contained in the sequence for the channel protein is necessary to understand the structural basis for some of the effects of the mutation. The experimental evidence supports the accuracy of the predicted structural model of the human heart Na(+) channel C-terminal domain and provides insight into a structural basis for some of the mutation-induced altered channel function underlying the disease phenotype.     

Structural Architecture of SNP Effects on Complex Traits

Despite the discovery of copy-number variation (CNV) across the genome nearly 10 years ago, current SNP-based analysis methodologies continue to collapse the homozygous (i.e., A/A), hemizygous (i.e., A/0), and duplicative (i.e., A/A/A) genotype states, treating the genotype variable as irreducible or unaltered by other colocalizing forms of genetic (e.g., structural) variation. Our understanding of common, genome-wide CNVs suggests that the canonical genotype construct might belie the enormous complexity of the genome. Here we present multiple analyses of several phenotypes and provide methods supporting a conceptual shift that embraces the structural dimension of genotype. We comprehensively investigate the impact of the structural dimension of genotype on (1) GWAS methods, (2) interpretation of rare LOF variants, (3) characterization of genomic architecture, and (4) implications for mapping loci involved in complex disease. Taken together, these results argue for the inclusion of a structural dimension and suggest that some portion of the “missing” heritability might be recovered through integration of the structural dimension of SNP effects on complex traits.     

Structural modifications of air-dried tendon collagen on heating

The modification of collagen molecular packing as a function of the removal of bound and structural water have been investigated on air-dried rat tail tendon. Isothermal curves, dilatometric measurement, high and small angle X-ray diffraction patterns—recorded using conventional and synchrotron radiaiton sources respectively—have been obtained on samples heated in air at different temperatures up to 200°C. A shortening of collagen intermolecular distances and slight modifications of quaternary structure and fibre dimensions can be observed during the release of bound water. The removal of structural water is accompanied by disordering of the three polypeptide chains, a strong reduction of fibre length and d-axial spacing, and modifications of the electron density distribution inside the repeating period. The structural modifications observed during the removal of bound water and of most of the structural water, obtained on heating, are reversible. Release of the most lightly bound water, probably associated with the beginning of the depolymerization process, induces irreversible modification of the molecular packing.     

基于结构变动度的不同付费方式住院医疗费用控制研究

目的 探讨住院医疗费用的结构构成,分析不同付费方式下影响费用结构变动的趋势与特征,为控制住院医疗费用不合理增长提供循证依据。方法 采用结构变动度、结构变动值和结构变动贡献率等指标进行统计分析。结果 住院医疗费用结构变动度达7.84%,以2012—2013年变动振幅较大;药品费、治疗费、化验费是引起结构变动的主要项目,三者累计贡献率为78.38%;其中化验费和治疗费呈持续正向变动,药品费呈持续负向变动。结论 控制住院医疗费用应结合不同付费方式分类制宜,药品费和检查化验费比重过高,而体现医护人员医疗服务价值的诊疗手术费等过低,费用结构有待优化,医疗服务价格与支付制度改革势在必行。     

放线菌素生物合成研究进展

放线菌素D是人类发现的第一个具有抗肿瘤活性的抗生素,但由于毒性太大,因而被限制用于几种恶性肿瘤治疗。本文概述了天然放线菌素的结构特点,重点介绍了放线菌素生物合成过程:犬尿氨酸途径,非核糖体肽合成途径和吩恶嗪酮发色团形成。对放线菌素生物合成途径的探索非常有利于开发新颖的低毒性的结构类似物。     

RNA structural motif recognition based on least-squares distance

RNA structural motifs are recurrent structural elements occurring in RNA molecules. RNA structural motif recognition aims to find RNA substructures that are similar to a query motif, and it is important for RNA structure analysis and RNA function prediction. In view of this, we propose a new method known as RNA Structural Motif Recognition based on Least-Squares distance (LS-RSMR) to effectively recognize RNA structural motifs. A test set consisting of five types of RNA structural motifs occurring in Escherichia coli ribosomal RNA is compiled by us. Experiments are conducted for recognizing these five types of motifs. The experimental results fully reveal the superiority of the proposed LS-RSMR compared with four other state-of-the-art methods.     

基于K-mer扭转角偏好的蛋白质结构类型预测

蛋白质的序列、结构和功能多种多样.大量研究表明蛋白质的结构与其氨基酸序列的排序有关,并且局部的氨基酸序列环境对蛋白质的结构具有一定的影响.本文提出一种新的基于5-mer氨基酸扭转角统计偏好的蛋白质结构类型预测方法,在该方法通过PDB数据库中5-mer中间氨基酸的扭转角统计偏好来进行结构类型的预测.新方法可以通过计算机仿...     

Atomistic simulations on interwall sliding behaviour of double-walled carbon nanotube: effects of structural defects

In this study, we investigated the interwall sliding behaviours of double-wall carbon nanotubes (DWCNTs) using molecular dynamics (MD) simulations, focusing on the effects of different structural defects including the vacancy, adsorbed atom (Adatom) and Stone-Wales (SW) defects. The simulation results showed that structural defects, especially the Adatom ones, caused large fluctuations and decreased the overall pull-out force. Stick-slip motions were observed in the interwall sliding processes of DWCNTs containing multiple structural defects. Among three types of structural defects, the Adatom defects most significantly weaken the interwall load transferring capability and degrade the interface shear strength (IFSS). This work provides useful information for promoting DWCNTs’ applications in Micro/Nano Electro-Mechanical Systems (M/NEMS).     

一类新内含子的研究状况

在真核细胞基因组中发现一类新内含子——AT-AC内含子, 除结构特征与普遍存在的核mRNA前体内含子有明显不同外,剪接机制上也存在一定差异.文章介绍了该内含子的分布,结构特征及剪接机理,并与主内含子作了相应比较.