molecular model

分子模型
  • 文章类型: Review
    淀粉样蛋白相关神经退行性疾病,包括阿尔茨海默病(AD),其特征是β-折叠结构的蛋白质聚集体在大脑中积累,称为淀粉样蛋白。然而,既没有建立疾病模型,也没有建立治疗方法。我们回顾过去的数据,并提出新的,帮助解决这个问题的初步数据和意见。以下是数据衍生的模型/假设。(1)淀粉样蛋白形成蛋白具有通过转换为另一种片状构象而实现的先天免疫功能,α片。(2)在健康方面,α-片结构,淀粉样蛋白通过与微生物α-片共组装来灭活微生物。淀粉样蛋白形成蛋白然后经历α-至β-折叠的转化。(3)在疾病中,α-片状结构,淀粉样蛋白形成蛋白过度积累并具有神经元毒性。该假设包括由α-折叠的病毒衣壳亚基形成。支持,我们发现5-10mM亚甲蓝(MB)在54℃时具有超膨胀,对噬菌体T4衣壳的减薄作用,在通过天然凝胶电泳(AGE)进行初始检测后,通过阴性染色和低温电子显微镜观察到。鉴于据报道MB的轻度抗AD作用,我们提出以下推论假设。(1)抗ADMB活动是,至少在某种程度上,由MB与淀粉样蛋白α-片层结合引起,并且(2)MB诱导T4衣壳亚基向α-片层的转变。我们建议使用药物孵育T4的AGE来测试改善的抗AD活性。
    Amyloid-associated neurodegenerative diseases, including Alzheimer\'s disease (AD), are characterized by the in-brain accumulation of β-sheet structured protein aggregates called amyloids. However, neither a disease model nor therapy is established. We review past data and present new, preliminary data and opinions to help solve this problem. The following is the data-derived model/hypothesis. (1) Amyloid-forming proteins have innate immunity functions implemented by conversion to another sheet conformation, α-sheet. (2) In health, α-sheet structured, amyloid-forming proteins inactivate microbes by co-assembly with microbe α-sheets. Amyloid-forming proteins then undergo α-to-β-sheet conversion. (3) In disease, α-sheet-structured, amyloid-forming proteins over-accumulate and are neuron-toxic. This hypothesis includes formation by virus capsid subunits of α-sheets. In support, we find that 5-10 mM methylene blue (MB) at 54 °C has a hyper-expanding, thinning effect on the phage T4 capsid, as seen by negative stain- and cryo-electron microscopy after initial detection by native gel electrophoresis (AGE). Given the reported mild anti-AD effect of MB, we propose the following corollary hypothesis. (1) Anti-AD MB activity is, at least in part, caused by MB-binding to amyloid α-sheet and (2) MB induces the transition to α-sheet of T4 capsid subunits. We propose using AGE of drug incubated T4 to test for improved anti-AD activity.
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  • 文章类型: Journal Article
    柑橘红螨Panorychuscitri对杀螨剂具有很强的抗性。细胞色素P450单加氧酶(P450)可以使农药解毒,并参与许多昆虫的农药抗性。这里,一株对吡啶甲酸耐性的柠檬酸假单胞菌菌株对cyenopyrafen具有交叉抗性,bifenazate,芬焦肟,还有Tolfenpyrad.胡椒基丁醚,P450抑制剂,可显着增加吡啶对抗性(Pyr_Rs)和易感(Pyr_Control)的毒性。Pyr_Rs中的P450活性明显高于Pyr_Control。对RNA-Seq数据的分析鉴定了P450基因(CYP4CL2),其可能与吡啶甲酸抗性有关。始终如一,它在两个田间抗性种群(CQ_WZ和CQ_TN)中上调。RNA干扰介导的CYP4CL2基因敲低可显著降低柑橘对吡啶甲酸的耐药性。表达CYP4CL2的转基因果蝇显示出增加的吡啶甲酸抗性。分子对接分析表明,吡啶甲酸可以在CYP4CL2的底物识别位点与几个氨基酸结合。这些发现揭示了P450介导的吡啶甲酸在害虫螨中的抗性。
    The citrus red mite Panonychus citri has developed strong resistance to acaricides. Cytochrome P450 monooxygenases (P450s) can detoxify pesticides and are involved in pesticide resistance in many insects. Here, a pyridaben-resistant P. citri strain showed cross-resistance to cyenopyrafen, bifenazate, fenpyroximate, and tolfenpyrad. Piperonyl butoxide, a P450 inhibitor, significantly increased the toxicity of pyridaben to resistant (Pyr_Rs) and susceptible (Pyr_Control) P. citri strains. P450 activity was significantly higher in Pyr_Rs than in Pyr_Control. Analyses of RNA-Seq data identified a P450 gene (CYP4CL2) that is potentially involved in pyridaben resistance. Consistently, it was up-regulated in two field-derived resistant populations (CQ_WZ and CQ_TN). RNA interference-mediated knockdown of CYP4CL2 significantly decreased the pyridaben resistance in P. citri. Transgenic Drosophila melanogaster expressing CYP4CL2 showed increased pyridaben resistance. Molecular docking analysis showed that pyridaben could bind to several amino acids at substrate recognition sites in CYP4CL2. These findings shed light on P450-mediated pyridaben resistance in pest mites.
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  • 文章类型: Journal Article
    硅藻是水生环境中突出且高度多样化的微藻。与其他硅藻物种相比,三角phaeodactylum是一种“非典型硅藻”,表现出三种不同的形态,并且缺乏通常的二氧化硅壳。尽管生态相关性有限,它在实验室和众所周知的生理学中容易生长,随着基因组信息的稳步增加,以及操纵基因表达的有效工具,这意味着它作为硅藻分子研究的强大实验模型获得了越来越多的认可。我们在这里简要概述了在过去的25年中,Tricornutum为揭示硅藻生物学的基本方面做出了贡献,同时也成为藻类过程工程和合成生物学的新工具。
    Diatoms are prominent and highly diverse microalgae in aquatic environments. Compared with other diatom species, Phaeodactylum tricornutum is an \"atypical diatom\" displaying three different morphotypes and lacking the usual silica shell. Despite being of limited ecological relevance, its ease of growth in the laboratory and well-known physiology, alongside the steady increase in genome-enabled information coupled with effective tools for manipulating gene expression, have meant it has gained increased recognition as a powerful experimental model for molecular research on diatoms. We here present a brief overview of how over the last 25 years P. tricornutum has contributed to the unveiling of fundamental aspects of diatom biology, while also emerging as a new tool for algal process engineering and synthetic biology.
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  • 文章类型: Journal Article
    堆肥溶解的有机物(DOM)是氧化还原活性有机分子的复杂混合物,会影响土壤环境中的各种生物地球化学过程。然而,化学复杂性(异质性和化学多样性)对DOM分子的电子接受能力(EAC)和电子供体能力(EDC)的影响尚不清楚。这阻碍了我们预测它们的环境行为和氧化还原特性的能力。在这项研究中,基于FT-ICRMS数据,验证了维也纳土壤有机质Modeler2(VSOMM2)对堆肥系统的适用性。开发了使用VSOMM2和Schrödinger软件的分子建模方法,以定量评估堆肥DOM的氧化还原位点和分子相互作用。堆肥DOM分子基于其异质来源被分为三个不同的组。此外,基于分子与EAC/EDC的联系,我们开发了18种堆肥DOM的分子模型。最后,Ar-OH,醌,Ar-SH,和Ar-NH2被确定为氧化还原位点;非共价接触,H债券,盐桥,芳香H键可能是堆肥DOM的重要电子传输通道。我们的发现有助于发展堆肥DOM中功能分子的精确调控方法,为符合特定生态系统服务要求的堆肥提供精细标准。
    Compost dissolved organic matter (DOM) is a complex mixture of redox-active organic molecules that impact various biogeochemical processes in soil environments. However, the impact of chemical complexity (heterogeneity and chemodiversity) on the electron accepting capacity (EAC) and electron donating capacity (EDC) of DOM molecules remains unclear, which hinders our ability to predict their environmental behavior and redox properties. In this study, the applicability of Vienna Soil Organic Matter Modeler 2 (VSOMM2) to the composting system based on the FT-ICR MS data has been validated. A molecular modeling approach using VSOMM2 and Schrödinger software was developed to quantitatively assess the redox sites and molecular interactions of compost DOM. Compost DOM molecules are categorized into three distinct groups based on their heterogeneous origins. In addition, we have developed 18 molecular models of compost DOM based on the links of molecules to EAC/EDC. Finally, Ar-OH, quinone, Ar-SH, and Ar-NH2 were identified as the redox sites; noncovalent contacts, H bonds, salt bridges, and aromatic-H bonds might be significant electronic transmission channels of compost DOM. Our findings contribute to the development of precise regulatory methods for functional molecules within compost DOM, providing the fine standards for composts matching specific ecosystem service requirements.
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  • 文章类型: Journal Article
    Siglecs是在不同类型的免疫细胞中发现的重要凝集素,并且通过识别自身缔合的聚糖并将细胞外相互作用转化为抑制免疫细胞功能的信号而充当调节分子。尽管已经发现许多Siglecs表现出广泛的特异性并识别不同类型的硫酸化寡糖,Siglec-8和Siglec-9对唾液酸N-乙酰乳糖胺(slacNAc)具有高度的特异性,在半乳糖(6'-硫酸化)和N-乙酰葡糖胺(6-硫酸化)的O6位进行硫酸化,分别。Siglec-3最近被发现结合SLacNAc两种硫酸化。除了与唾液酸残基结合的保守精氨酸残基,CC环中的序列多样性可以提供对Siglecs中硫酸化寡糖的结合特异性。因此,本研究采用分子模型来研究Siglec-8/9/3的CC环中不同残基对sLacNAc的Gal和/或GlcNAc中6-硫酸化的识别的影响。Siglec-9的CC环中带负电荷的残基与Gal中的6-硫酸盐形成了不利的静电排斥,并且没有识别,与Siglec-8的CC'环中带正电荷的残基和Gal中的6-硫酸盐之间形成的有利相互作用相反,产生强特异性。提出了一种两态结合模型,用于Siglec-3识别sLacNAc的Gal和GlcNAc中的6-硫酸化,因为Siglec-3的CC\'环中的中性残基不能形成强烈的有利相互作用以将Gal中的6-硫酸盐锁定在单个结合姿势内或强烈的不利相互作用以排斥Gal中的6-硫酸盐。寡糖采用两种独特的结合姿势,并使硫酸基团定向以与CC'环和G链中的残基形成相互作用。本研究为Siglec-8/9/3的CC'环中的序列多样性确定了对硫酸化寡糖的识别提供了结构机制,并提供了对Siglecs结合特异性的见解。
    Siglecs are important lectins found in different types of immune cells and function as regulatory molecules by recognizing self-associated glycans and converting extracellular interactions into signals for inhibiting immune cell functions. Although many Siglecs have been found to show broad specificities and recognize different types of sulfated oligosaccharides, Siglec-8 and Siglec-9 displayed a high degree of specificity for sialyl N-acetyllactosamine (sLacNAc) with sulfations at O6-positions of the galactose (6\'-sulfation) and N-acetylglucosamine (6-sulfation), respectively. Siglec-3 was recently discovered to bind sLacNAc both sulfations. In addition to a conserved arginine residue for binding to sialic acid residue, the sequence variety in the CC\' loop may provide binding specificities to sulfated oligosaccharides in Siglecs. Thus, the present study employed molecular models to study the impact of different residues in the CC\' loops of Siglec-8/9/3 to the recognitions of 6-sulfations in Gal and/or GlcNAc of sLacNAc. The negatively charged residues in the CC\' loop of Siglec-9 formed unfavorable electrostatic repulsions with the 6-sulfate in Gal and resulted no recognitions, in contrast to the favorable interactions formed between the positively charged residues in the CC\' loop of Siglec-8 and the 6-sulfate in Gal resulting strong specificity. A two-state binding model was proposed for Siglec-3 recognizing 6-sulfations in Gal and GlcNAc of sLacNAc, as the neutral residues in the CC\' loop of Siglec-3 could not form strong favorable interactions to lock the 6-sulfate in Gal within a single binding pose or strong unfavorable interactions to repel the 6-sulfate in Gal. The oligosaccharide adopted two distinctive binding poses and oriented the sulfate groups to form interactions with residues in the CC\' loop and G-strand. The present study provided a structural mechanism for the sequence variety in the CC\' loop of Siglec-8/9/3 determining the recognitions to the sulfated oligosaccharides and offered insights into the binding specificities for Siglecs.
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  • 文章类型: Journal Article
    Carbon nanotubes (CNTs) are nanometer-sized structures that can be used to reinforce cement matrices. The extent to which the mechanical properties are improved depends on the interfacial characteristics of the resulting materials, that is, on the interactions established between the CNTs and the cement. The experimental characterization of these interfaces is still impeded by technical limitations. The use of simulation methods has a great potential to give information about systems lacking experimental information. In this work, molecular dynamics (MD) and molecular mechanics (MM) were used in conjunction with finite element simulations to study the interfacial shear strength (ISS) of a structure formed by a pristine single-walled CNT (SWCNT) inserted in a tobermorite crystal. The results show that, for a constant SWCNT length, ISS values increase when the SWCNT radius increases, while for a constant SWCNT radius, shorter lengths enhance ISS values.
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  • 文章类型: Journal Article
    用含解旋酶C结构域的蛋白1(IFIH1)基因诱导的干扰素编码胞质RNA解旋酶,也称为黑色素瘤分化相关5(MDA5),RIG-1样RNA解旋酶,其识别病毒RNA并通过识别病毒RNA而参与先天免疫。在与双链(ds)RNA结合时,MDA5沿着dsRNA的长度形成丝状组装体,并利用分子特征来区分自我,相对于基于dsRNA长度和甲基化的非自身。它的错义变体rs35667974对1型糖尿病具有保护作用,牛皮癣,和银屑病关节炎,但也发现与强直性脊柱炎的风险增加有关,克罗恩病,和溃疡性结肠炎.为了深入了解该变体的复杂作用,我们使用分子动力学模拟对具有dsRNA的复合物中的MDA5进行了结构分析。我们的数据表明,虽然rs35667974变体的Ile923Val突变不会显着影响与天然dsRNA的结合,在存在2'-O尿苷甲基化的情况下,它表现出不稳定作用。因此,dsRNA上2'-O-甲基化的存在引入了传感信号,导致整体MDA催化活性的选择性降低。这项研究代表了对自身免疫基因座IFIH1的共享rs35667974变体的作用的评估,据报道导致修饰的MDA5表型的催化活性选择性降低,因此,减少对细胞因子和趋化因子信号的负反馈,并选择性地保护免受自身免疫。
    Interferon induced with helicase C domain-containing protein 1 (IFIH1) gene encodes a cytoplasmic RNA helicase otherwise known as melanoma differentiation-associated 5 (MDA5), a RIG-1-like RNA helicase that recognizes viral RNA and is involved in innate immunity through recognition of viral RNA. Upon binding to double-stranded (ds) RNA, MDA5 forms a filamentous assembly along the length of dsRNA and utilizes molecular signatures to discriminate self, versus non-self on the basis of dsRNA length and methylation. Its missense variant rs35667974 is protective for type 1 diabetes, psoriasis, and psoriatic arthritis, but is also found to be associated with an increased risk for ankylosing spondylitis, Crohn\'s disease, and ulcerative colitis. To gain insight into the complex role of this variant we performed a structural analysis of MDA5 in complex with dsRNA using molecular dynamics simulations. Our data suggest that while the Ile923Val mutation of the rs35667974 variant does not affect binding to native dsRNA significantly, it displays a destabilizing effect in the presence of 2\'-O uridine methylation. Thus, the presence of 2\'-O-methylation at the dsRNA introduces a sensing signature that leads to selective reduction of the overall MDA catalytic activity. This study represents an evaluation of the role of the shared rs35667974 variant of autoimmune locus IFIH1, reported to lead to selectively reduced catalytic activity of the modified MDA5 phenotype and, as a consequence, reduced negative feedback on cytokine and chemokine signaling and selectively protection against autoimmunity.
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  • 文章类型: Journal Article
    土壤溶解有机质(DOM)由土壤溶液中大量复杂的有机化合物组成,并显着影响土壤环境中的一系列(生物)地球化学过程。然而,化学复杂性如何(即,土壤DOM分子的异质性和化学多样性)对其质子和金属结合能力的影响尚不清楚,这限制了我们预测DOM和金属环境行为的能力。在这项研究中,基于Cu滴定实验,我们开发了一种统一的建模方法来量化土壤DOM的质子和金属结合能力,傅里叶变换离子回旋共振质谱数据,和分子建模方法。尽管来自不同地区的土壤DOM样品具有极大的异质性和多样性,我们发现土壤DOM的分子可以根据其Cu结合能力分为三个代表组。根据单个分子群的分子模型和每个土壤DOM中每个分子群的相对贡献,我们能够进一步开发所有土壤DOM的分子模型,以预测其分子性质以及质子和金属结合能力。我们的结果将有助于开发机械模型,以预测各种来源的土壤DOM的反应性。
    Soil dissolved organic matter (DOM) is composed of a mass of complex organic compounds in soil solutions and significantly affects a range of (bio)geochemical processes in soil environment. However, how the chemical complexity (i.e., heterogeneity and chemodiversity) of soil DOM molecules affects their proton and metal binding ability remains unclear, which limits our ability for predicting the environmental behavior of DOM and metals. In this study, we developed a unified modeling approach for quantifying the proton and metal binding ability of soil DOM based on Cu titration experiments, Fourier transform ion cyclotron resonance mass spectrometry data, and molecular modeling method. Although soil DOM samples from different regions have enormously heterogeneous and diverse properties, we found that the molecules of soil DOM can be divided into three representative groups according to their Cu binding capacity. Based on the molecular models for individual molecular groups and the relative contributions of each group in each soil DOM, we were able to further develop molecular models for all soil DOM to predict their molecular properties and proton and metal binding ability. Our results will help to develop mechanistic models for predicting the reactivity of soil DOM from various sources.
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  • 文章类型: Journal Article
    暂无摘要。
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  • 文章类型: Journal Article
    开花时间对于生存和繁殖至关重要。李属属于玫瑰科,包括数百种开花树木和灌木,具有重要的观赏和经济价值。然而,李属早期开花的分子机制尚不清楚。这里,我们利用梅花和桃花的基因组和转录组探索早期开花的转录调控机制。比较基因组学发现,占总P.mu基因组92.4%和总P.serica基因组91.2%的基因属于正统。在P.mume和P.persica之间共发现19,169个正统,包括20,431个相应的直系同源物和20,080个共线性基因对。共发现305个与早期开花相关的差异表达基因(DEGs),其中FT,TLI65和NAP57被鉴定为早期开花调节途径中的枢纽基因。此外,我们从9个蛋白质家族中鉴定出25个转录因子(TFs),包括MADS-box,AP2/ERF,还有MYB.我们的结果提供了对李属开花时间调节的潜在分子模型的见解,并强调了多组学在破译属间植物特性中的实用性。
    Flowering time is crucial for the survival and reproduction. Prunus genus belongs to the Rosaceae family and includes several hundred species of flowering trees and shrubs with important ornamental and economic values. However, the molecular mechanism underlying early flowering in Prunus genus is unclear. Here, we utilized the genome and transcriptome of P. mume and P. persica to explore the transcriptional regulation mechanism of early flowering. Comparative genomics found that genes accounting for 92.4% of the total P. mume genome and 91.2% of the total P. persica genome belonged to orthogroups. A total of 19,169 orthogroups were found between P. mume and P. persica, including 20,431 corresponding orthologues and 20,080 collinearity gene pairs. A total of 305 differentially expressed genes (DEGs) associated with early flowering were found, among which FT, TLI65, and NAP57 were identified as hub genes in the early flowering regulation pathway. Moreover, we identified twenty-five transcription factors (TFs) from nine protein families, including MADS-box, AP2/ERF, and MYB. Our results provide insights into the underlying molecular model of flowering time regulation in Prunus genus and highlight the utility of multi-omics in deciphering the properties of the inter-genus plants.
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