检索结果-南通市图书馆

Altered hACE2 binding affinity and S1/S2 cleavage efficiency of SARS-CoV-2 spike protein mutants affect viral cell entry

引用

Virologica Sinica 2023年第4期38卷 595-605页

作者： Ke Wang Yu Pan Dianbing Wang Ye Yuan Min Li Yuanyuan Chen Lijun Bi Xian-En Zhang National Key Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing100101China Faculty of Synthetic Biology Shenzhen Institute of Advanced TechnologyShenzhen518055China University of Chinese Academy of Sciences Beijing100101China

SARS-CoV-2 variants are constantly emerging,hampering public health measures in controlling the number of infections.While it is well established that mutations in spike proteins observed for the different variants directly affect virus entry into host cells,there remains a need for further expansion of systematic and multifaceted comparisons.Here,we comprehensively studied the effect of spike protein mutations on spike expression and proteolytic activation,binding affinity,viral entry efficiency and host cell tropism of eight variants of concern(VOC)and variants of interest(VOI).We found that both the full-length spike and its receptor-binding domain(RBD)of Omicron bind to hACE2 with an affinity similar to that of the wild-type.In addition,Alpha,Beta,Delta and Lambda pseudoviruses gained significantly enhanced cell entry ability compared to the wild-type,while the Omicron pseudoviruses showed a slightly increased cell entry,suggesting the vastly increased rate of transmission observed for Omicron variant is not associated with its affinity to hACE2.We also found that the spikes of Omicron and Mu showed lower S1/S2 cleavage efficiency and inefficiently utilized TMPRSS2 to enter host cells than others,suggesting that they prefer the endocytosis pathway to enter host cells.Furthermore,all variants'pseudoviruses we tested gained the ability to enter the animal ACE2-expressing cells.Especially the infection potential of rats and mice showed significantly increased,strongly suggesting that rodents possibly become a reservoir for viral evolution.The insights gained from this study provide valuable guidance for a targeted approach to epidemic control,and contribute to a better understanding of SARS-CoV-2 evolution.

关键词： SARS-CoV-2 Variants of Concern(VOC) Omicron binding affinity Viral entry Host-tropism

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

A Deep Learning Drug-Target binding affinity Prediction Based on Compound Microstructure and Its Application in COVID-19 Drug Screening

引用

Journal of Beijing Institute of Technology 2023年第4期32卷 396-405页

作者： Yijie Guo Xiumin Shi Han Zhou School of Information and Electronics Beijing Institute of TechnologyBeijing 100081China

Drug target relationship(DTR)prediction is a rapidly evolving area of research in com-putational drug discovery.Despite recent advances in computational solutions that have overcome the challenges of in vitro and in vivo experiments,most computational methods still focus on binary classification.They ignore the importance of binding affinity,which correctly distinguishes between on-targets and off-targets.In this study,we propose a deep learning model based on the microstruc-ture of compounds and proteins to predict drug-target binding affinity(DTA),which utilizes topo-logical structure information of drug molecules and sequence semantic information of proteins.In this model,graph attention network(GAT)is used to capture the deep features of the compound molecular graph,and bidirectional long short-term memory(BiLSTM)network is used to extract the protein sequence features,and the pharmacological context of DTA is obtained by combining the two.The results show that the proposed model has achieved superior performance in both cor-rectly predicting the value of interaction strength and correctly discriminating the ranking of bind-ing strength compared to the state-of-the-art baselines.A case study experiment on COVID-19 con-firms that the proposed DTA model can be used as an effective pre-screening tool in drug discovery.

关键词： compound microstructure drug-target interaction binding affinity deep learning COVID-19

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Computational Assessment of Protein–protein binding affinity by Reversely Engineering the Energetics in Protein Complexes

引用

Genomics, Proteomics & Bioinformatics 2021年第6期19卷 1012-1022页

作者： Bo Wang Zhaoqian Su Yinghao Wu Department of Systems and Computational Biology Albert Einstein College of MedicineBronxNY 10461USA

The cellular functions of proteins are maintained by forming diverse complexes.The stability of these com-plexes is quantified by the measurement of binding affinity,and mutations that alter the binding affinity can cause various diseases such as cancer and diabetes.As a result,accurate estimation of the binding stability and the effects of mutations on changes of binding affinity is a crucial step to understanding the biological functions of proteins and their dysfunctional consequences.It has been hypothesized that the stability of a protein complex is dependent not only on the residues at its binding interface by pairwise interactions but also on all other remaining residues that do not appear at the binding interface.Here,we computationally reconstruct the binding affinity by decomposing it into the contributions of interfacial residues and other non-interfacial residues in a protein complex.We further assume that the contributions of both interfacial and non-interfacial residues to the binding affinity depend on their local structural environments such as solvent-accessible surfaces and secondary structural types.The weights of all corresponding parameters are optimized by Monte-Carlo simulations.After cross-validation against a large-scale dataset,we show that the model not only shows a strong correlation between the absolute values of the experimental and calculated binding affinities,but can also be an effective approach to predict the relative changes of binding affinity from mutations.Moreover,we have found that the optimized weights of many parameters can capture the first-principle chemical and physical features of molecular recognition,therefore re-versely engineering the energetics of protein complexes.These results suggest that our method can serve as a useful addition to current computational approaches for predicting binding affinity and understanding the molecular mechanism of protein–protein interactions.

关键词： Protein-protein interaction binding affinity Non-interfacial residue Knowledge-based potential Monte-Carlo simulation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Expression and functional characterization of odorant-binding protein 2 in the predatory mite Neoseiulus barkeri

引用

Insect Science 2023年第5期30卷 1493-1506页

作者： Yixia Wu Yaying Li Wenqiang Chu Tiandi Niu Xiaotian Feng Rongjiang Ma Huai Liu Key Laboratory of Entomology and Pest Control Engineering College of Plant ProtectionSouthwest UniversityBeibei DistrictChongqing400715 China

Olfaction plays a crucial role for arthropods in foraging,mating,and oviposition.The odorant-binding protein(OBP)gene is considered one of the most important olfactory genes.However,little is known about its functions in predatory mites.Here,we used Neoseiulus barkeri,an important commercialized natural pest control,to explore the chemosensory characteristics of OBP.In this study,N.barkeri was attracted by methyl salicylate(MeSA)and showed higher crawling speeds under MeSA treatment.Then,we identified and cloned an OBP gene named Nbarobp2 and analyzed its expression profiles in the predatory mite.Nbarobp2 was 663 bp,was highly expressed in larval and nymphal stages,and was significantly upregulated in N.barkeri under MeSA treatment.Nbarobp2 encoded 202 amino acid residues with a molecular weight of 23 kDa(after removing the signal peptide).Sequence comparisons revealed that the OBPs in Arachnida shared 6 conserved cysteine sites,but were distinguishable from the OBPs of Insecta on the phylogenetic tree.RNA interference,Western blotting,and binding affinity assays further proved that Nbarobp2 was involved in volatile perception in predatory mites.This study shed light on the functional characteristics of OBPs in predatory mites,providing a new insight for better biological control.

关键词： binding affinity crawling speed heterologous expression methyl salicylate olfactory behavior RNA interference

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Principles of amino-acid–ribonucleotide interaction revealed by binding affinities between homogeneous oligopeptides and singlestranded RNA molecules

引用

Nano Research 2023年第12期16卷 13294-13300页

作者： Pengyu Wang Xiaocui Fang Ping Li Minxian Li Yanlian Yang Chen Wang Key Laboratory for Biological Effects of Nanomaterials and Nanosafety(Chinese Academy of Sciences(CAS)) Key Laboratory of Standardization and Measurement for Nanotechnology(CAS)CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

We have determined the binding strengths between ribonucleotides of adenine(A),guanine(G),uracil(U),and cytosine(C)in homogeneous single-stranded ribonucleic acids(ssRNAs)and homo-decapeptides consisting of 20 common amino acids.We use a bead-based fluorescence assay for these measurements in which decapeptides are immobilized on the bead surface and ssRNAs are in solutions.The results provide a molecular basis for analyzing selectivity,specificity,and polymorphisms of amino-acid–ribonucleotide interactions.Comparative analyses of the distribution of the binding energies reveal unique binding strength patterns assignable to each pair of amino acid and ribonucleotide originating from the chemical structures.Pronounced favorable(such as Arg–G)and unfavorable(such as Met–U)binding interactions can be identified in selected groups of amino acid and ribonucleotide pairs that could provide basis to elucidate energetics of amino-acid–ribonucleotide interactions.Such interaction selectivity,specificity,and polymorphism manifest the contributions from RNA backbone,RNA bases,as well as main chain and side chain of the amino acids.Such characteristics in peptide–RNA interactions might be helpful for understanding the mechanism of protein–RNA specific recognition and the design of RNA nano-delivery systems based on peptides and their derivatives.

关键词： peptides single-stranded ribonucleic acid(ssRNA) binding affinity flow cytometry

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Quantifying phase separation at the nanoscale by dual-color fluorescence cross-correlation spectroscopy(dcFCCS)

引用

Biophysics Reports 2022年第1期8卷 29-41页

作者： Yirong Yao Wenjuan Wang Chunlai Chen Beijing Frontier Research Center of Biological Structure Tsinghua University Beijing Advanced Innovation Center for Structural Biology School of Life Sciences Technology Center for Protein Sciences Tsinghua University

Liquid–liquid phase separation(LLPS) causes the formation of membraneless condensates, which play important roles in diverse cellular processes. Currently, optical microscopy is the most commonly used method to visualize micron-scale phase-separated condensates. Because the optical spatial resolution is restricted by the diffraction limit(～200 nm), dynamic formation processes from individual biomolecules to micron-scale condensates are still mostly unknown. Herein, we provide a detailed protocol applying dual-color fluorescence cross-correlation spectroscopy(dcFCCS) to detect and quantify condensates at the nanoscale, including their size, growth rate, molecular stoichiometry, and the binding affinity of client molecules within condensates. We expect that the quantitative dcFCCS method can be widely applied to investigate many other important phase separation systems.

关键词： Liquid-liquid phase separation Nanoscale Dual-color fluorescence cross-correlation spectroscopy Molecular stoichiometry binding affinity

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Principles of fluorescence correlation spectroscopy applied to studies of biomolecular liquid–liquid phase separation

引用

Biophysics Reports 2022年第2期8卷 100-118页

作者： Zhulou Wang Huizhi Zhang Lin Jian Bo Ding Keying Huang Wolun Zhang Qian Xiao Shaohui Huang Institute of Biophysics Chinese Academy of Sciences LightEdge Technologies Limited School of Life Sciences University of Chinese Academy of Sciences

Fluorescence correlation spectroscopy(FCS) investigates the temporal relationship of fluctuating fluorescence signals reflecting underlying molecular processes occurring in a solution sample or a single live cell. This review article introduces the principles of two basic and most used FCS techniques: fluorescence auto-correlation spectroscopy(FACS) and fluorescence cross-correlation spectroscopy(FCCS). Combined, FACS and FCCS techniques can quantitatively analyze multiple properties of molecule or nanoparticle samples, including molar concentration, diffusion coefficient and hydrodynamic radius, homo-or hetero-interaction, fluorescence brightness, etc. Not surprisingly, FCS techniques have long been used to investigate molecular mechanisms of biomolecular phase separation, first in the lipid bilayer and more recently in cell cytosol and nucleoplasm. The latter applications are especially exciting since a whole new class of membraneless cellular organelles have been discovered, which are proposed to be results of biomolecule liquid-liquid phase separation(LLPS). LLPS research can benefit significantly from the multifunctionality and single-molecule sensitivity of a variety of FCS techniques,particularly for live-cell studies. This review illustrates how FACS and FCCS techniques can be used to investigate multiple aspects of the molecular mechanisms of LLPS, and summarizes FCS applications to LLPS research in vivo and in vitro.

关键词： Liquid–liquid phase separation Fluorescence correlation spectroscopy Diffusion coefficient Hydrodynamic radius binding affinity

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

A simple fluorescence anisotropy assay for detection of bisphenol A using fluorescently labeled aptamer

引用

Journal of Environmental Sciences 2020年第11期32卷 19-24页

作者： Liying Liu Qiang Zhao State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China

Bisphenol A(BPA)is one of the environmental endocrine disruptors(EDCs),and BPA contamination in environment can cause high risks to human health.Rapid determination of BPA on sites is in high demand in environmental analysis.Taking advantage of aptamers as affinity ligands and fluorescence anisotropy(FA)analysis,we developed a simple and rapid FA assay for BPA by employing a single tetramethylrhodamine(TMR)labeled short 35-mer DNA aptamer against BPA.The assay is based on the BPA-binding induced conformation change of TMR-labeled aptamer and alteration of interaction between TMR and guanine bases,resulting in change of FA signals.We screened the FA change of aptamer probes having TMR label on a specific site of the aptamer upon BPA addition.The aptamer with a TMR label on the 22nd T base showed large FA-decreasing response to BPA and maintained good binding affinity to BPA.By using this TMR-labeled aptamer,we achieved FA detection of BPA with a detection limit of 0.5μmol/L under the optimized conditions.This assay was selective towards BPA and enabled the detection of BPA spiked in tap water sample,showing the potential applications on water samples.

关键词： Bisphenol A Aptamer Fluorescence anisotropy Fluorescence polarization Microscale thermophoresis binding affinity

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

“补丁”生长模式:利用炔基配体调控金-金界面

引用

Science China Materials 2022年第6期65卷 1687-1695页

作者：宗建鹏任权田晓丽项停冯宇华陈虹宇 Institute of Advanced Synthesis(IAS) School of Chemistry and Molecular EngineeringJiangsu National Synergetic Innovation Centre for Advanced MaterialsNanjing Tech UniversityNanjing 211816China School of Science Westlake UniversityHangzhou 310023China Institute of Natural Sciences Westlake Institute for Advanced StudyHangzhou 310024China

表面配体在纳米合成中起着关键作用,扩大适用于纳米合成的配体范围具有重要意义.本工作中,我们系统研究了炔基配体在金种子上生长金时对金-金界面的调节作用.我们观察到了一种新的“补丁”生长模式:具有孔洞以及分支的金补丁“平躺”在... 详细信息

表面配体在纳米合成中起着关键作用,扩大适用于纳米合成的配体范围具有重要意义.本工作中,我们系统研究了炔基配体在金种子上生长金时对金-金界面的调节作用.我们观察到了一种新的“补丁”生长模式:具有孔洞以及分支的金补丁“平躺”在金种子表面.这种生长模式与传统的弱配体控制的晶面生长以及强配体调控下的非润湿岛状生长截然不同.通过控制炔基配体的分子结构及其在金种子表面的排列,生长的金可以从补丁形状连续调节到岛状,同时其等离子体共振吸收从可见光区扩展到了近红外光谱区域.我们相信这类具有中等强度、能够控制特殊生长模式的新配体的应用,能够显著提升纳米合成及应用中的配体控制作用.

关键词： phenynyls binding affinity Au patch ligand packing Au-Au hybrids

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

High affinity soluble ILT2 receptor:a potent inhibitor of CD8^(+)T cell activation

引用

Protein & Cell 2010年第12期1卷 1118-1127页

作者： Ruth K.Moysey Yi Li Samantha J.Paston Emma E.Baston Malkit S.Sami Brian J.Cameron Jessie Gavarret Penio Todorov Annelise Vuidepot Steven M.Dunn Nicholas J.Pumphrey Katherine J.Adams Fang Yuan Rebecca E.Dennis Deborah H.Sutton Andy D.Johnson Joanna E.Brewer Rebecca Ashfield Nikolai M.Lissin Bent K.Jakobsen Immunocore Limited 57c Milton ParkAbingdonOxonOX144RXUK Current address:Oxford Nanopore Technologies UK Current address:Geneva Merck Serono S.A. Switzerland Current address:Adaptimmune Limited UK

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin superfamily receptor ILT2(synonyms:LIR1,MIR7,CD85j),we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex(MHC)class I molecules.Produced in a dimeric form,either by chemical cross-linking with bivalent polyethylene glycol(PEG)derivatives or as a genetic fusion with human IgG Fc-fragment,the mutants exhibited a further increase in ligand-binding strength due to the avidity effect,with resident half-times(t1/2)on the surface of MHC I-positive cells of many hours.The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors(TCRs).In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8^(+)cytotoxic T lymphocytes(CTLs)in the presence of their target cells,with subnanomolar potency and in a dose-dependent manner.As a selective inhibitor of CD8^(+)CTL responses,the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.

关键词： CD8^(+)T cells cellular activation autoimmunity cell surface molecules binding affinity phage display

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：