发布求助
文献互助 智能选刊 最新文献

Current opinion in structural biology最新文献

筛选
英文 中文
Navigating protein–nucleic acid sequence-structure landscapes with deep learning 用深度学习导航蛋白质核酸序列结构景观
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-12-01 Epub Date: 2025-09-22 DOI: 10.1016/j.sbi.2025.103162
Elodie Laine , Sergei Grudinin , Roman Klypa , Isaure Chauvot de Beauchêne
{"title":"Navigating protein–nucleic acid sequence-structure landscapes with deep learning","authors":"Elodie Laine ,&nbsp;Sergei Grudinin ,&nbsp;Roman Klypa ,&nbsp;Isaure Chauvot de Beauchêne","doi":"10.1016/j.sbi.2025.103162","DOIUrl":"10.1016/j.sbi.2025.103162","url":null,"abstract":"<div><div>A few years after AlphaFold revolutionised the field of protein structure prediction, the new frontiers and limitations in structural biology have become clearer. Predicting protein–nucleic acid interactions currently stands as one of the major unresolved challenges in the field. This knowledge gap stems from the scarcity and limited diversity of experimental data, as well as the unique geometric, physicochemical, and evolutionary properties of nucleic acids. Despite these challenges, innovative ideas and promising methodological developments have emerged for both predicting protein–nucleic acid complex structures and designing nucleic acids capable of binding to specific protein conformations. This review presents these recent advances and discusses promising avenues, including the integration of high-throughput profiling data, the development of more rigourous and richer evaluation benchmarks, and the discovery of biologically meaningful regulatory and structural signals using self-supervised learning.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103162"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118931","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
Advances in automation for cryo-electron tomography data collection 低温电子断层成像数据采集自动化研究进展。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-12-01 Epub Date: 2025-11-24 DOI: 10.1016/j.sbi.2025.103192
Kedar Sharma, Mario J. Borgnia
{"title":"Advances in automation for cryo-electron tomography data collection","authors":"Kedar Sharma,&nbsp;Mario J. Borgnia","doi":"10.1016/j.sbi.2025.103192","DOIUrl":"10.1016/j.sbi.2025.103192","url":null,"abstract":"<div><div>Cryo-electron microscopy has become the preferred method for determining structures of macromolecular complexes both in isolation, using single particle analysis, and in their cellular contexts, using cryo-electron tomography (Cryo-ET) combined with subvolume averaging (SVA). Collection of tilt series for Cryo-ET introduces challenges such as low signal-to-noise ratios, sample radiation sensitivity, and mechanical imprecision of the microscope stage – particularly at high magnifications. Strategies to improve throughput and resolution include continuous tilt and beam-image-shift parallel acquisition, real-time predictive adjustments, and machine learning-driven targeting. Additionally, montage tomography has increased the observable cellular area, while innovations like rectangular condenser apertures promise improved dose efficiency. Web-based and machine learning-enhanced solutions for automated and remote microscope operation are improving the user experience. Collectively, these advancements represent a critical step towards robust, high-resolution, and user-friendly Cryo-ET, facilitating the visualization of macromolecular assemblies within their authentic biological environments.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103192"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602864","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
Dynamic characteristics of proteolysis-targeting chimera systems revealed by in silico computations 用计算机计算揭示蛋白水解靶向嵌合体系统的动态特性。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-12-01 Epub Date: 2025-09-10 DOI: 10.1016/j.sbi.2025.103151
Kexin Xu , Jingxuan Ge , Rongfan Tang , Tingjun Hou , Huiyong Sun
{"title":"Dynamic characteristics of proteolysis-targeting chimera systems revealed by in silico computations","authors":"Kexin Xu ,&nbsp;Jingxuan Ge ,&nbsp;Rongfan Tang ,&nbsp;Tingjun Hou ,&nbsp;Huiyong Sun","doi":"10.1016/j.sbi.2025.103151","DOIUrl":"10.1016/j.sbi.2025.103151","url":null,"abstract":"<div><div>Proteolysis-targeting chimeras (PROTACs) achieve irreversible clearance of target proteins by hijacking the ubiquitin–proteasome system, breaking the design paradigm of traditional inhibitory drugs. The development of computational approaches has effectively promoted the rational design of PROTACs, yet existing methods mainly focus on predicting the static structure of PROTAC systems, with methodological gaps in analyzing their dynamic characteristics. Knowing that the dynamic behaviors can dramatically influence the stability and degradation efficacy of a PROTAC system, we systematically summarize the recent progresses of using structure-based and structure–artificial intelligence–hybrid methodologies for characterizing the dynamic behaviors of PROTAC systems, with a focus on elucidating the dynamic characteristics of target protein–PROTAC–E3 ligase ternary structures and prediction of their key properties.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103151"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039512","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
From snapshots to ensembles: Integrating experimental data and dynamics 从快照到集成：整合实验数据和动力学
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-12-01 Epub Date: 2025-09-15 DOI: 10.1016/j.sbi.2025.103155
Vanessa Leone , Fabrizio Marinelli
{"title":"From snapshots to ensembles: Integrating experimental data and dynamics","authors":"Vanessa Leone ,&nbsp;Fabrizio Marinelli","doi":"10.1016/j.sbi.2025.103155","DOIUrl":"10.1016/j.sbi.2025.103155","url":null,"abstract":"<div><div>Protein function arises from the interplay of structure, dynamics, and biomolecular interactions. Despite advances in cryo-EM and AI-based structure prediction, capturing dynamic and energetic features remains a challenge. Biophysical methods like NMR, EPR, HDX-MS, SAXS, and cryo-EM provide valuable but often indirect signals. Connecting these to molecular mechanisms requires integrative approaches that combine experiments with physics-based simulations, revealing both stable structures and transient, functionally important intermediates. This review highlights recent advances in integrative modeling using the maximum entropy principle to build dynamic ensembles from diverse data while addressing uncertainty and bias. These methods help resolve heterogeneity and interpret low-resolution data. We conclude by exploring how integrative modeling, enhanced sampling, and AI-driven tools enable new insights into slow, large-scale conformational changes.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103155"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060742","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
Allosteric solution to the problems of undruggable targets, drug toxicity, and emerging resistance 变构解决问题的不可药物的目标，药物毒性，和新出现的耐药性
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-12-01 Epub Date: 2025-10-23 DOI: 10.1016/j.sbi.2025.103172
Wei-Ven Tee , Igor N. Berezovsky
{"title":"Allosteric solution to the problems of undruggable targets, drug toxicity, and emerging resistance","authors":"Wei-Ven Tee ,&nbsp;Igor N. Berezovsky","doi":"10.1016/j.sbi.2025.103172","DOIUrl":"10.1016/j.sbi.2025.103172","url":null,"abstract":"<div><div>Though allostery is a well-established research field, its importance for biomedical applications, spanning from the allosteric effects of mutations in diagnostics to the design of innovative allosteric drugs, is yet to be fully appreciated. The potential of allostery in resolving issues of current drug design and in targeting proteins considered difficult or undruggable is the main topic of this review. In particular, we discuss how the non-conservatism of allosteric sites enables selective targeting of individual members in conserved families, thereby minimizing off-target toxicity. The multiplicity of allosteric sites in any structure allows alleviation of challenges posed by emerging drug resistance driven by allosteric and orthosteric mutations. The modulatory action of allosteric drugs provides, at the same time, an important therapeutic advantage in gradual activation/inhibition of enzymatic function and signaling in receptors. We also discuss here an approach for rational design of allosteric drugs, illustrating its process and output in obtaining effectors with the above-mentioned advantages and characteristics. Reviewing recent advances in the development of allosteric effectors, we show that allostery is undoubtedly becoming an integral part of the drug discovery paradigm. We, therefore, anticipate that the pharmaceutical industry will be prompted to systematically incorporate allostery as an important complement to existing drug design strategies in the near future.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103172"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358158","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
Chromatin as a three-dimensional memory machine 染色质是三维记忆机器
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-12-01 Epub Date: 2025-10-04 DOI: 10.1016/j.sbi.2025.103160
Jeremy A. Owen , Leonid A. Mirny
{"title":"Chromatin as a three-dimensional memory machine","authors":"Jeremy A. Owen ,&nbsp;Leonid A. Mirny","doi":"10.1016/j.sbi.2025.103160","DOIUrl":"10.1016/j.sbi.2025.103160","url":null,"abstract":"<div><div>Epigenetic memory—the stable inheritance of a cellular state over cell generations—has long been associated with chromatin modifications. But individual modifications are very dynamic. How can they carry information across cell generations? Recent theoretical work suggests the answer might lie, in part, in the three-dimensional organization of the genome. Cooperation between marks brought together by genome folding can correct epigenetic errors, making stable memory units out of unstable marks. If marks direct the phase separation of chromatin, the resulting bidirectional coupling between marks and structure provides a mechanism for many of these units to operate independently along the genome. Models of bidirectional coupling have helped identify elements, such as formation of a dense compartment, 3D mark spreading, and limited enzyme, which may be key to stable epigenetic memory. An analogy between these 3D models and a classic model of associative memory hints at a way chromatin could perform sophisticated information processing.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103160"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217985","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
Dictionary based approaches for studying intrinsic DNA shape in transcription factor recognition 基于字典的转录因子识别中DNA固有形状研究方法
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-12-01 Epub Date: 2025-10-04 DOI: 10.1016/j.sbi.2025.103166
Manisha Kalsan, Sadiya Mirza, Divyangana Bathla, Shandar Ahmad
{"title":"Dictionary based approaches for studying intrinsic DNA shape in transcription factor recognition","authors":"Manisha Kalsan,&nbsp;Sadiya Mirza,&nbsp;Divyangana Bathla,&nbsp;Shandar Ahmad","doi":"10.1016/j.sbi.2025.103166","DOIUrl":"10.1016/j.sbi.2025.103166","url":null,"abstract":"<div><div>Sequence-dependent <em>intrinsic</em> conformational dynamics confer specificity to transcriptional factor recognition of genomic DNA. Their genome-scale investigation using all-atom simulations is challenging, and alternative approaches by coarse-graining DNA into beads-and-sticks or polymer models have their own limitations. One parallel approach is what we describe here as a dictionary-based approach. This has been shown to explain several transcriptional events in biological systems but has been inadequately reviewed. These approaches represent studies based on a finite number of DNA fragments and their corresponding conformational properties, scaled up to genomes by pooling nearby fragments and machine learning models. This article aims to organize efforts made in generating these models and their recent successful applications to stimulate further development of this approach.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103166"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217986","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
Drug targeting of protein-nucleic acid interactions 蛋白质-核酸相互作用的药物靶向。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-12-01 Epub Date: 2025-10-07 DOI: 10.1016/j.sbi.2025.103165
Luca R. Genz , Sanjana Nair , Aaron Sweeney , Maya Topf
{"title":"Drug targeting of protein-nucleic acid interactions","authors":"Luca R. Genz ,&nbsp;Sanjana Nair ,&nbsp;Aaron Sweeney ,&nbsp;Maya Topf","doi":"10.1016/j.sbi.2025.103165","DOIUrl":"10.1016/j.sbi.2025.103165","url":null,"abstract":"<div><div>Protein–nucleic acid interactions are vital to gene regulation and disease, yet have long been considered “undruggable.” Recent advances are reshaping this paradigm, enabling therapeutic targeting of DNA- and RNA-binding proteins. In this review, we highlight four major strategies: (1) direct disruption of protein-nucleic acid binding, (2) stabilization of specific complexes or conformations, (3) targeted degradation of interaction partners, and (4) allosteric modulation. We explore key examples across transcription factors, RNA-binding proteins, and DNA repair proteins, and emphasize emerging chemical, structural, and computational techniques that are accelerating discovery. Together, by intervening directly in the gene regulatory machinery, these approaches expand the druggable genome and open new avenues for treating cancer, genetic disorders, and viral infections.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103165"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250262","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
Ras/Raf dimerization model for activation of Raf kinase 激活Raf激酶的Ras/Raf二聚化模型
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-12-01 Epub Date: 2025-09-09 DOI: 10.1016/j.sbi.2025.103150
Marcela de Barros, Gregory Labrie, Carla Mattos
{"title":"Ras/Raf dimerization model for activation of Raf kinase","authors":"Marcela de Barros,&nbsp;Gregory Labrie,&nbsp;Carla Mattos","doi":"10.1016/j.sbi.2025.103150","DOIUrl":"10.1016/j.sbi.2025.103150","url":null,"abstract":"<div><div>Our previously proposed Ras dimerization model is consistent with recent details observed by NMR in that Raf activation is centered on the Ras/Raf dimer, distinct from one in which Ras activates Raf as a monomer with the Raf cysteine rich domain inserted in the membrane. We review mechanistic understanding of Raf activation within nanoclusters of Ras on the membrane, with a shift to dimers upon binding Raf. This sets the stage for a signaling platform composed of Ras/Raf and Galectin dimers that facilitates the release of Raf autoinhibition and folding of the Raf intrinsically disordered region between the Ras-binding domains and the kinase bound to 14-3-3 and MEK. This platform could provide synchronized units for signal amplification and is consistent with a Ras stationary phase observed in cells.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103150"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020928","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
Chromatin higher-order folding as influenced by preferred values of linker DNA 染色质高阶折叠受连接体DNA偏好值的影响。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-12-01 Epub Date: 2025-09-19 DOI: 10.1016/j.sbi.2025.103154
Zilong Li , Stephanie Portillo-Ledesma , Tamar Schlick
{"title":"Chromatin higher-order folding as influenced by preferred values of linker DNA","authors":"Zilong Li ,&nbsp;Stephanie Portillo-Ledesma ,&nbsp;Tamar Schlick","doi":"10.1016/j.sbi.2025.103154","DOIUrl":"10.1016/j.sbi.2025.103154","url":null,"abstract":"<div><div>Specific values of nucleosome spacing have long been associated with distinct chromatin organization, but recent studies reveal surprising structural and functional consequences of small changes in regular linker DNA length. This opinion article revisits experimental and modeling studies addressing the classic 10<em>n</em> versus 10<em>n</em> + 5 spacing, highlighting how this 5 bp difference can alter nucleosome orientation, fiber topology, and higher-order chromatin behavior. We underscore how differences in model parameters and system design yield different trends for the effect of linker DNA lengths on chromatin architecture. However, chromatin structure <em>in vivo</em> reflects the heterogeneous nucleosome spacing in combination with other cellular variables like salt conditions, epigenetic marks, and protein and RNA binding, which work together to shape gene folding and direct gene regulation.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103154"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102550","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
首页 上一页 下一页 尾页
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整，为了账户安全，请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们：info@booksci.cn Book学术提供免费学术资源搜索服务，方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号：604180095
Book学术官方微信
小红书