Nucleic Acids Research最新文献

PockFlex: a web server for flexibility-aware binding site identification and prioritisation from structural ensembles. PockFlex：一个web服务器，用于从结构集成中识别灵活性感知的结合位点和优先级。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2026-05-08 DOI: 10.1093/nar/gkag453

Inés S Rahali, Yacine Serir, Kheira Rahali, Delphine Flatters, Leslie Regad, Anne-Claude Camproux

{"title":"PockFlex: a web server for flexibility-aware binding site identification and prioritisation from structural ensembles.","authors":"Inés S Rahali, Yacine Serir, Kheira Rahali, Delphine Flatters, Leslie Regad, Anne-Claude Camproux","doi":"10.1093/nar/gkag453","DOIUrl":"https://doi.org/10.1093/nar/gkag453","url":null,"abstract":"PockFlex is a web server designed to analyse pockets across protein structural ensembles and support the reconstruction, characterisation, and prioritisation of recurrent binding site organisations. Applicable to ensembles derived from molecular dynamics simulations, multiple experimental structures, or protein structure predictions, PockFlex detects pockets independently in each conformation, retains those overlapping a user-defined region of interest, and groups them across the ensemble by residue-level similarity. This residue-centred clustering framework identifies recurrent binding site clusters, quantifies residue recurrence and variability, and distinguishes persistent from transient binding site regions across the ensemble. Pocket-level druggability, predicted using the PockDrug workflow, is summarised at the cluster level to support binding site prioritisation under conformational variability while preserving access to individual pocket scores. The web application provides interactive, residue-level insights into pocket organisation, variability, and druggability in structural ensembles. The web server is free and open to all users, without login requirement, at https://pockflex.rpbs.univ-paris-diderot.fr/.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DAVID: a web server for functional annotation and functional enrichment analysis of gene lists (2025 update). DAVID：用于基因列表功能注释和功能富集分析的web服务器（2025年更新）。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2026-05-08 DOI: 10.1093/nar/gkag470

Brad T Sherman, Ganesh Panzade, Thoai Dotrang, Ming Hao, Lei Xu, Xuan Li, Michael W Baseler, H Clifford Lane, Tomozumi Imamichi, Weizhong Chang

{"title":"DAVID: a web server for functional annotation and functional enrichment analysis of gene lists (2025 update).","authors":"Brad T Sherman, Ganesh Panzade, Thoai Dotrang, Ming Hao, Lei Xu, Xuan Li, Michael W Baseler, H Clifford Lane, Tomozumi Imamichi, Weizhong Chang","doi":"10.1093/nar/gkag470","DOIUrl":"https://doi.org/10.1093/nar/gkag470","url":null,"abstract":"DAVID is a widely used bioinformatics resource that provides functional annotation and functional enrichment analysis for gene and protein lists derived from high-throughput studies. It integrates a comprehensive gene-centered knowledgebase with a suite of web-accessible analytical tools. Since its initial release in 2003, DAVID developments have been published in 12 papers and cited >80 000 times. Here, we report updates made since the previous NAR Web Server Issue publication in 2022. This update introduces two new tools: DAVID Ortholog for cross-species functional analysis and DAVID Gene Search for identifier-agnostic gene exploration, modernizes the web interface, and implements a new backend architecture that decouples the frontend from the legacy Java processing engine. A new Servlet layer and REST APIs enable asynchronous processing and support integration of a Neo4j graph database for relationship-based queries. Major existing tools have been redesigned with modern, interactive interfaces, and multiformat result export. The pathway viewer has been redesigned with interactive drag-and-zoom navigation, animated user gene highlighting, and publication-quality downloads. Collectively, these updates enhance performance and usability, and the new backend architecture enables independent evolution of frontend and backend components while maintaining continuity with legacy analyses. DAVID remains freely available at https://davidbioinformatics.nih.gov without login.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

T2T-Hub: a central platform for analyzing plant and animal telomere-to-telomere genomes. T2T-Hub：分析植物和动物端粒到端粒基因组的中心平台。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2026-05-06 DOI: 10.1093/nar/gkag423

Haoyu Chao, Zhonghao Ruan, Zhuojin Li, Xinkai Zhou, Shilong Zhang, Xingxing Shen, Cong Feng, Dijun Chen, Ming Chen

{"title":"T2T-Hub: a central platform for analyzing plant and animal telomere-to-telomere genomes.","authors":"Haoyu Chao, Zhonghao Ruan, Zhuojin Li, Xinkai Zhou, Shilong Zhang, Xingxing Shen, Cong Feng, Dijun Chen, Ming Chen","doi":"10.1093/nar/gkag423","DOIUrl":"https://doi.org/10.1093/nar/gkag423","url":null,"abstract":"T2T-Hub is a free, web-based platform designed to facilitate the analysis and visualization of telomere-to-telomere (T2T) genomes in plants and animals. The server integrates automated structural and functional annotation workflows with interactive visualization and comparative analysis tools, enabling systematic exploration of complete genome assemblies. T2T-Hub provides a standardized and unified analytical framework specifically tailored for T2T genomes, enabling consistent and comparable analyses across species. To ensure robustness and comparability, we uniformly analyzed 230 high-quality plant and 39 animal T2T genomes using the same standardized workflows, providing users with a consistent reference framework. Users can upload assembled T2T genome sequences together with gene annotation files (GFF3), which are automatically validated and processed through unified analyses including genome quality assessment, telomere and centromere identification, transcription factor prediction, functional annotation, and interactive genome visualization. Importantly, the platform enables interactive genome browsing, searching, and result sharing without requiring any programming skills, thereby lowering the barrier for T2T genome analysis. For internally curated genomes, T2T-Hub additionally provides repeat and noncoding RNA annotation, comparative genomics analyses, and integrated online tools. The platform is freely accessible without login at https://bis.zju.edu.cn/t2thub and https://biobigdata.nju.edu.cn/t2thub.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ligify 2.0: a web server for predicted small molecule biosensors. Ligify 2.0：用于预测小分子生物传感器的web服务器。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2026-05-06 DOI: 10.1093/nar/gkag458

Simon d'Oelsnitz, Nicole N Zhao, Pranay Talla, Jio Jeong, Joshua D Love, Michael Springer, Pamela A Silver

{"title":"Ligify 2.0: a web server for predicted small molecule biosensors.","authors":"Simon d'Oelsnitz, Nicole N Zhao, Pranay Talla, Jio Jeong, Joshua D Love, Michael Springer, Pamela A Silver","doi":"10.1093/nar/gkag458","DOIUrl":"https://doi.org/10.1093/nar/gkag458","url":null,"abstract":"Prokaryotic transcription factors (TFs) serve as small molecule biosensors with broad applications in biotechnology, yet only a fraction have been characterized. To address this gap, we recently described the bioinformatic method Ligify, which leverages information from genome context and enzyme reaction databases to predict a TF's cognate effector molecule. Here, we report Ligify 2.0, a modern web server for Ligify predictions. We systematically evaluate 10 965 small molecules within the Rhea enzyme reaction database for associations to TFs, ultimately generating 13 435 hypothetical interactions between 1 362 small molecules and 3 164 TFs. We then develop an interactive web server (https://ligify.groov.bio) to search and visualize prediction data. Each TF sensor page includes visualizations for chemical ligand structures, interactive TF protein structures, and genome context. Pages also include metadata links, predicted promoter sequences, prediction confidence metrics, and references to relevant literature. A plasmid builder tool enables users to generate custom biosensor circuit designs. Finally, we provide case studies using Ligify 2.0 to identify two TFs from the pathogens Escherichia coli O157:H7 and Mycobacterium abscessus responsive to 4-hydroxybenzoate and Pseudomonas Quinolone Signal, respectively. The Ligify web server aims to facilitate the systematic characterization of biosensors for chemical-control of biological systems.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CB-Dock3: an enhanced web server for protein-ligand blind docking. CB-Dock3：用于蛋白质与配体盲对接的增强型web服务器。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2026-05-06 DOI: 10.1093/nar/gkag417

Yang Liu, Ji Ding, Jianhong Gan, Xiaoman Xiong, Fanjie Zong, Zhi-Xiong Xiao, Yang Cao

{"title":"CB-Dock3: an enhanced web server for protein-ligand blind docking.","authors":"Yang Liu, Ji Ding, Jianhong Gan, Xiaoman Xiong, Fanjie Zong, Zhi-Xiong Xiao, Yang Cao","doi":"10.1093/nar/gkag417","DOIUrl":"https://doi.org/10.1093/nar/gkag417","url":null,"abstract":"Elucidating protein-ligand interactions is pivotal for understanding biological mechanisms and accelerating drug discovery. Blind docking, which identifies binding sites without prior knowledge, has become an indispensable computational strategy for analyzing the surge of protein structures generated by Cryo-EM and AI-based prediction tools like AlphaFold3. Our previous server, CB-Dock2, has been widely adopted by the global research community, averaging over 1000 daily submissions since July 2022 due to its accuracy and user-friendliness. Building on this foundation and incorporating extensive user feedback, we present CB-Dock3, a substantially enhanced platform. Key upgrades include a refined docking engine, an expanded template library, and support for diverse file formats. Benchmark evaluations on CASF-2016 demonstrate that CB-Dock3 achieves a success rate of 67.4% (RMSD ≤ 2.0 Å), representing a 10.6 percentage-point absolute improvement over its predecessor and outperforming other popular blind docking tools. Additionally, CB-Dock3 introduces critical new features driven by community needs: support for user-defined docking regions to handle large complexes, and a metal-aware protocol that explicitly retains essential metal ions and cofactors during simulation. CB-Dock3 stands as an accurate, rapid, and accessible resource for the scientific community, freely available at https://cadd.labshare.cn/cb-dock3/.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ARTEM server: an online tool for nucleic acid 3D motif searches, 3D structure superposition and structure-based alignment. ARTEM服务器：用于核酸三维基序搜索、三维结构叠加和基于结构的比对的在线工具。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2026-05-05 DOI: 10.1093/nar/gkag428

Dominik Sordyl, Jan Cielesz, Davyd R Bohdan, Eugene F Baulin, Janusz M Bujnicki

{"title":"ARTEM server: an online tool for nucleic acid 3D motif searches, 3D structure superposition and structure-based alignment.","authors":"Dominik Sordyl, Jan Cielesz, Davyd R Bohdan, Eugene F Baulin, Janusz M Bujnicki","doi":"10.1093/nar/gkag428","DOIUrl":"https://doi.org/10.1093/nar/gkag428","url":null,"abstract":"ARTEM Server is an online platform for comparative analysis of nucleic acid 3D structures, combining two complementary superposition methods based on the ARTEM algorithm. The server provides access to searches for local tertiary motifs using the ARTEM tool, which identifies local isosteric structural arrangements without relying on sequence, interaction annotations, or backbone connectivity. It also offers global structure alignment and search modes via ARTEMIS, a recent extension of ARTEM that performs global sequence alignments based on rigid-body structural superposition. ARTEMIS supports both classical sequentially ordered superpositions and alignments involving sequence permutations, and can enumerate alternative suboptimal matches, enabling structural searches within large molecules or across databases. Benchmarks reported in the original publications demonstrate that ARTEM and ARTEMIS outperform other tools and are particularly effective at detecting 3D motif and 3D fold similarities across diverse backbone contexts, including cases that are challenging for sequence-ordered or annotation-dependent methods. ARTEM Server unifies these capabilities in a web interface, accepting PDB/mmCIF inputs, supporting multiple query and reference structures, and providing interactive 3D visualization and exportable alignment and motif-matching data. ARTEM Server offers a user-friendly web-based environment for exploration of global nucleic acid folds and local tertiary motifs. The web server is available at https://artemserver.genesilico.pl/.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation of precise and accurate engineered circRNAs using enzymatic ligation. 使用酶连接产生精确和精确的工程环状rna。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2026-05-05 DOI: 10.1093/nar/gkag405

Amrita Singh, Adela Dujsikova, Noah Mueller, Y Grace Chen

{"title":"Generation of precise and accurate engineered circRNAs using enzymatic ligation.","authors":"Amrita Singh, Adela Dujsikova, Noah Mueller, Y Grace Chen","doi":"10.1093/nar/gkag405","DOIUrl":"https://doi.org/10.1093/nar/gkag405","url":null,"abstract":"messenger RNA-based therapeutics have revolutionized the treatment and prevention of infectious, neurological, and cancer diseases. However, their linear topology makes them susceptible to rapid degradation in vivo, which limits their therapeutic efficacy. Engineered circular RNAs (circRNAs) due to their closed ends and high stability are emerging as a promising alternative to linear RNA therapies. Engineered circRNAs are also increasingly used to mimic naturally occurring circRNAs in functional studies. Both applications, however, depend on production of precise circRNAs with homogenous sequences to enable accurate interpretation of biological outcomes. To address this, we developed and optimized methods for generating precise circRNAs. We employed enzymatic ligation of linear RNAs rather than autocatalytic splicing to produce circRNAs to minimize extraneous nucleotides remaining from the ribozymes. We carefully designed the DNA transcription template to maintain sequence and structural integrity. A permuted DNA template leveraging three internal guanosines (Gs) was synthesized and amplified using a reverse primer containing two 2'-O-methyl groups. This approach optimally produced the linear precursor RNA with correct 5' and 3' ends. After testing multiple workflows, we found that GMP-primed in vitro transcription, T4 RNA ligase 2-mediated circularization, and urea-polyacrylamide gel electrophoresis (PAGE) gel extraction produced the highest fidelity circRNAs.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"54 9","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and biochemical characterization of yeast Tcd enzymes installing the post-transcriptional modification ct6A in tRNA. 在tRNA中安装转录后修饰ct6A的酵母Tcd酶的结构和生化特性。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2026-05-05 DOI: 10.1093/nar/gkag376

Julia Hirschmann, Rachel Sonntag, Matthias Heiss, Ewa Wegrzyn, Wolfgang Heinemeyer, Thomas Carell, Eva M Huber

{"title":"Structural and biochemical characterization of yeast Tcd enzymes installing the post-transcriptional modification ct6A in tRNA.","authors":"Julia Hirschmann, Rachel Sonntag, Matthias Heiss, Ewa Wegrzyn, Wolfgang Heinemeyer, Thomas Carell, Eva M Huber","doi":"10.1093/nar/gkag376","DOIUrl":"10.1093/nar/gkag376","url":null,"abstract":"Post-transcriptional modifications near the anticodon of transfer ribonucleic acids (tRNAs) ensure translation fidelity and accuracy. For instance, at position 37, the universally conserved and essential nucleoside N6-threonylcarbamoyladenosine (t6A) supports decoding of ANN triplets. In some organisms t6A is converted to cyclic t6A (ct6A), but only little is known about this ATP-dependent reaction and the corresponding threonylcarbamoyladenosine dehydratases (Tcds). We here show that yeast Tcds localize to the outer mitochondrial membrane and co-purify with tRNAs recognizing ANN codons. Depending on the number of TCD genes in the genome, the proteins form V-shaped hetero- or homodimers, of which at least one subunit binds and modifies tRNAs. The C-terminal, monomeric domain shares similarities with Cas9-endonucleases and assists tRNA recognition, while the N-terminal domain mediates dimerization and contains the active site. Structure-based mutagenesis and activity assays imply that yeast Tcds lack a catalytic cysteine and do not covalently bind their substrate as proposed for Escherichia coli TcdA.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"54 9","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to 'Directed evolution of hyperactive integrases for site specific insertion of transgenes'. 更正“针对转基因位点特异性插入的过度活跃整合酶的定向进化”。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2026-05-05 DOI: 10.1093/nar/gkag492

引用次数: 0

Retraction of 'NicOPURE: nickless RNA circularization and one-step purification with engineered group II introns and cyclizing UTRs'. 撤回“NicOPURE：无镍RNA环化和一步纯化工程II族内含子和环化utr”。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2026-05-05 DOI: 10.1093/nar/gkag467

引用次数: 0