Journal of Molecular Biology最新文献

Species-specific model based on sequence and structural information for ubiquitination sites prediction 基于序列和结构信息的泛素化位点预测物种特异性模型。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2024-09-07 DOI: 10.1016/j.jmb.2024.168781

{"title":"Species-specific model based on sequence and structural information for ubiquitination sites prediction","authors":"","doi":"10.1016/j.jmb.2024.168781","DOIUrl":"10.1016/j.jmb.2024.168781","url":null,"abstract":"<div><p>Ubiquitination is a common post-translational modification of proteins in eukaryotic cells, and it is also a significant method of regulating protein biological function. Computational methods for predicting ubiquitination sites can serve as a cost-effective and time-saving alternative to experimental methods. Existing computational methods often build classifiers based on protein sequence information, physical and chemical properties of amino acids, evolutionary information, and structural parameters. However, structural information about most proteins cannot be found in existing databases directly. The features of proteins differ among species, and some species have small amounts of ubiquitinated proteins. Therefore, it is necessary to develop species-specific models that can be applied to datasets with small sample sizes. To solve these problems, we propose a species-specific model (SSUbi) based on a capsule network, which integrates proteins’ sequence and structural information. In this model, the feature extraction module is composed of two sub-modules that extract multi-dimensional features from sequence and structural information respectively. In the submodule, the convolution operation is used to extract encoding dimension features, and the channel attention mechanism is used to extract feature map dimension features. After integrating the multi-dimensional features from both types of information, the species-specific capsule network further converts the features into capsule vectors and classifies species-specific ubiquitination sites. The experimental results show that SSUbi can effectively improve the prediction performance of species with small sample sizes and outperform other models.</p></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152892","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 Basis of Main Proteases of Coronavirus Bound to Bofutrelvir 冠状病毒主要蛋白酶与 Bofutrelvir 结合的结构基础。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2024-09-06 DOI: 10.1016/j.jmb.2024.168784

{"title":"Structural Basis of Main Proteases of Coronavirus Bound to Bofutrelvir","authors":"","doi":"10.1016/j.jmb.2024.168784","DOIUrl":"10.1016/j.jmb.2024.168784","url":null,"abstract":"<div><p>Globally, the continuous spread and evolution of SARS-CoV-2, along with its variants, profoundly impact human well-being, health, security, and the growth of socio-economic. In the field of development of drugs against COVID-19, the main protease (M<sup>pro</sup>) is a critical target as it plays a core role in the lifecycle of SARS-CoV-2. Bofutrelvir acts as a potent inhibitor of SARS-CoV-2 M<sup>pro</sup>, demonstrating high efficacy and broad-spectrum antiviral activity. Compared to therapies that require pharmacokinetic boosters, such as ritonavir, the monotherapy approach of Bofutrelvir reduces the risk of potential drug interactions, making it suitable for a wider patient population. However, further studies on the potency and mechanism of inhibition of Bofutrelvir against the M<sup>pro</sup> of COVID-19 and its variants, together with other coronaviruses, are needed to prepare for the possibility of a possible re-emerging threat from an analogous virus in the future. Here, we reveal the effective inhibition of Bofutrelvir against the M<sup>pro</sup> of SARS-CoV-2, SARS-CoV, and HCoV-229E through FRET and crystallographic analysis. Furthermore, the inhibitory mechanisms of Bofutrelvir against two SARS-CoV-2 M<sup>pro</sup> mutants (G15S and K90R) were also elucidated through FRET and crystallographic studies. Through detailed analysis and comparison of these crystal structures, we identified crucial structural determinants of inhibition and elucidated the binding mode of Bofutrelvir to M<sup>pro</sup>s from different coronaviruses. These findings are hopeful to accelerate the development of safer and more potent inhibitors against the M<sup>pro</sup> of coronavirus, and to provide important references for the prevention and treatment of similar viruses that may emerge in the future.</p></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152893","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

Accurate Identification of Periplasmic Urea-binding Proteins by Structure- and Genome Context-assisted Functional Analysis 通过结构和基因组上下文辅助功能分析，准确鉴定外质尿素结合蛋白。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2024-09-04 DOI: 10.1016/j.jmb.2024.168780

{"title":"Accurate Identification of Periplasmic Urea-binding Proteins by Structure- and Genome Context-assisted Functional Analysis","authors":"","doi":"10.1016/j.jmb.2024.168780","DOIUrl":"10.1016/j.jmb.2024.168780","url":null,"abstract":"<div><p>ABC transporters are ancient and ubiquitous nutrient transport systems in bacteria and play a central role in defining lifestyles. Periplasmic solute-binding proteins (SBPs) are components that deliver ligands to their translocation machinery. SBPs have diversified to bind a wide range of ligands with high specificity and affinity. However, accurate assignment of cognate ligands remains a challenging problem in SBPs. Urea metabolism plays an important role in the nitrogen cycle; anthropogenic sources account for more than half of global nitrogen fertilizer. We report identification of urea-binding proteins within a large SBP sequence family that encodes diverse functions. By combining genetic linkage between SBPs, ABC transporter components, enzymes or transcription factors, we accurately identified cognate ligands, as we verified experimentally by biophysical characterization of ligand binding and crystallographic determination of the urea complex of a thermostable urea-binding homolog. Using three-dimensional structure information, these functional assignments were extrapolated to other members in the sequence family lacking genetic linkage information, which revealed that only a fraction bind urea. Using the same combined approaches, we also inferred that other family members bind various short-chain amides, aliphatic amino acids (leucine, isoleucine, valine), γ-aminobutyrate, and as yet unknown ligands. Comparative structural analysis revealed structural adaptations that encode diversification in these SBPs. Systematic assignment of ligands to SBP sequence families is key to understanding bacterial lifestyles, and also provides a rich source of biosensors for clinical and environmental analysis, such as the thermostable urea-binding protein identified here.</p></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022283624004005/pdfft?md5=356797fb37fbbeef8d8ff761fcd53192&pid=1-s2.0-S0022283624004005-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144764","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

Pause Patrol: Negative Elongation Factor's role in Promoter-Proximal Pausing and beyond. 暂停巡逻队：负延伸因子在启动子-近端暂停及其他过程中的作用

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2024-09-04 DOI: 10.1016/j.jmb.2024.168779

Annette J Diao, Bonnie G Su, Seychelle M Vos

引用次数: 0

RiboVision2: A Web Server for Advanced Visualization of Ribosomal RNAs RiboVision2：核糖体 RNA 高级可视化网络服务器

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2024-09-01 DOI: 10.1016/j.jmb.2024.168556

引用次数: 0

ModFOLD9: A Web Server for Independent Estimates of 3D Protein Model Quality ModFOLD9：独立评估三维蛋白质模型质量的网络服务器

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2024-09-01 DOI: 10.1016/j.jmb.2024.168531

{"title":"ModFOLD9: A Web Server for Independent Estimates of 3D Protein Model Quality","authors":"","doi":"10.1016/j.jmb.2024.168531","DOIUrl":"10.1016/j.jmb.2024.168531","url":null,"abstract":"<div><p>Accurate models of protein tertiary structures are now available from numerous advanced prediction methods, although the accuracy of each method often varies depending on the specific protein target. Additionally, many models may still contain significant local errors. Therefore, reliable, independent model quality estimates are essential both for identifying errors and selecting the very best models for further biological investigations. ModFOLD9 is a leading independent server for detecting the local errors in models produced by any method, and it can accurately discriminate between high-quality models from multiple alternative approaches. ModFOLD9 incorporates several new scores from deep learning-based approaches, leading to greatly improved prediction accuracy compared with earlier versions of the server. ModFOLD9 is continuously independently benchmarked, and it is shown to be highly competitive with other public servers. ModFOLD9 is freely available at <span><span>https://www.reading.ac.uk/bioinf/ModFOLD/</span><svg><path></path></svg></span>.</p></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022283624001189/pdfft?md5=9949e23171833ce240958abd18778192&pid=1-s2.0-S0022283624001189-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140152741","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

Alpha&ESMhFolds: A Web Server for Comparing AlphaFold2 and ESMFold Models of the Human Reference Proteome Alpha&ESMhFolds：用于比较人类参考蛋白质组的 AlphaFold2 和 ESMFold 模型的网络服务器。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2024-09-01 DOI: 10.1016/j.jmb.2024.168593

引用次数: 0

IHMCIF: An Extension of the PDBx/mmCIF Data Standard for Integrative Structure Determination Methods IHMCIF：整合结构确定方法的 PDBx/mmCIF 数据标准扩展。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2024-09-01 DOI: 10.1016/j.jmb.2024.168546

{"title":"IHMCIF: An Extension of the PDBx/mmCIF Data Standard for Integrative Structure Determination Methods","authors":"","doi":"10.1016/j.jmb.2024.168546","DOIUrl":"10.1016/j.jmb.2024.168546","url":null,"abstract":"<div><p>IHMCIF (<span><span>github.com/ihmwg/IHMCIF</span><svg><path></path></svg></span>) is a data information framework that supports archiving and disseminating macromolecular structures determined by integrative or hybrid modeling (IHM), and making them Findable, Accessible, Interoperable, and Reusable (<em>FAIR</em>). IHMCIF is an extension of the Protein Data Bank Exchange/macromolecular Crystallographic Information Framework (PDBx/mmCIF) that serves as the framework for the Protein Data Bank (PDB) to archive experimentally determined atomic structures of biological macromolecules and their complexes with one another and small molecule ligands (e.g., enzyme cofactors and drugs). IHMCIF serves as the foundational data standard for the PDB-Dev prototype system, developed for archiving and disseminating integrative structures. It utilizes a flexible data representation to describe integrative structures that span multiple spatiotemporal scales and structural states with definitions for restraints from a variety of experimental methods contributing to integrative structural biology. The IHMCIF extension was created with the benefit of considerable community input and recommendations gathered by the Worldwide Protein Data Bank (wwPDB) Task Force for Integrative or Hybrid Methods (<span><span>wwpdb.org/task/hybrid</span><svg><path></path></svg></span>). Herein, we describe the development of IHMCIF to support evolving methodologies and ongoing advancements in integrative structural biology. Ultimately, IHMCIF will facilitate the unification of PDB-Dev data and tools with the PDB archive so that integrative structures can be archived and disseminated through PDB.</p></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022283624001414/pdfft?md5=7a3e7aade30878dc264a3e57ea5efe5f&pid=1-s2.0-S0022283624001414-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178792","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

Leaf Senescence Database v5.0: A Comprehensive Repository for Facilitating Plant Senescence Research 叶片衰老数据库 v5.0：促进植物衰老研究的综合资料库。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2024-09-01 DOI: 10.1016/j.jmb.2024.168530

{"title":"Leaf Senescence Database v5.0: A Comprehensive Repository for Facilitating Plant Senescence Research","authors":"","doi":"10.1016/j.jmb.2024.168530","DOIUrl":"10.1016/j.jmb.2024.168530","url":null,"abstract":"<div><p>Through an extensive literature survey, we have upgraded the Leaf Senescence Database (LSD v5.0; <span><span>https://ngdc.cncb.ac.cn/lsd/</span><svg><path></path></svg></span>), a curated repository of comprehensive senescence-associated genes (SAGs) and their corresponding mutants. Since its inception in 2010, LSD undergoes frequent updates to encompass the latest advances in leaf senescence research and its current version comprises a high-quality collection of 31,740 SAGs and 1,209 mutants from 148 species, which were manually searched based on robust experimental evidence and further categorized according to their functions in leaf senescence. Furthermore, LSD was greatly enriched with comprehensive annotations for the SAGs through meticulous curation using both manual and computational methods. In addition, it was equipped with user-friendly web interfaces that facilitate text queries, BLAST searches, and convenient download of SAG sequences for localized analysis. Users can effortlessly navigate the database to access a plethora of information, including literature references, mutants, phenotypes, multi-omics data, miRNA interactions, homologs in other plants, and cross-links to various databases. Taken together, the upgraded version of LSD stands as the most comprehensive and informative plant senescence-related database to date, incorporating the largest collection of SAGs and thus bearing great utility for a wide range of studies related to plant senescence.</p></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022283624001177/pdfft?md5=4966a0c80ee9743534f4c43a1fe22860&pid=1-s2.0-S0022283624001177-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093171","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

TPPU_DSF: A Web Application to Calculate Thermodynamic Parameters Using DSF Data TPPU_DSF：利用 DSF 数据计算热力学参数的网络应用程序

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2024-09-01 DOI: 10.1016/j.jmb.2024.168519

{"title":"TPPU_DSF: A Web Application to Calculate Thermodynamic Parameters Using DSF Data","authors":"","doi":"10.1016/j.jmb.2024.168519","DOIUrl":"10.1016/j.jmb.2024.168519","url":null,"abstract":"<div><p>Here we present TPPU_DSF (<span><span>https://maciasnmr.net/tppu_dsf/</span><svg><path></path></svg></span>). This is a free and open-source web application that opens, converts, fits, and calculates the thermodynamic parameters of protein unfolding from standard differential scanning fluorimetry (DSF) data in an automated manner. The software has several applications. In the context of screening compound libraries for protein binders, obtaining thermodynamic parameters provides a more robust approach to detecting hits than the changes in the melting temperature (T<sub>m</sub>) alone, thereby helping to increase the number of positive hits in screening campaigns. Moreover, changes in ΔG<sub>u</sub><sup>o</sup> indicate protein response to binding at lower compound concentrations than those in the T<sub>m</sub>, thereby reducing the costs associated with the amounts of protein and compounds required for the assays. Also, by adding thermodynamic information to the T<sub>m</sub> comparison, the software can contribute to the optimization of protein constructs and buffer conditions, a common practice before structural and functional projects.</p></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022283624001062/pdfft?md5=cf58214544ee4ccc6fb33b70056879e3&pid=1-s2.0-S0022283624001062-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140099308","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