Pub Date : 2024-06-25DOI: 10.1016/j.sbi.2024.102871
Syeda Rehana Zia , Adriana Coricello , Giovanni Bottegoni
By incorporating full flexibility and enabling the quantification of crucial parameters such as binding free energies and residence times, methods for investigating protein-ligand binding and unbinding via molecular dynamics provide details on the involved mechanisms at the molecular level. While these advancements hold promise for impacting drug discovery, a notable drawback persists: their relatively time-consuming nature limits throughput. Herein, we survey recent implementations which, employing a blend of enhanced sampling techniques, a clever choice of collective variables, and often machine learning, strive to enhance the efficiency of new and previously reported methods without compromising accuracy. Particularly noteworthy is the validation of these methods that was often performed on systems mirroring real-world drug discovery scenarios.
{"title":"Increased throughput in methods for simulating protein ligand binding and unbinding","authors":"Syeda Rehana Zia , Adriana Coricello , Giovanni Bottegoni","doi":"10.1016/j.sbi.2024.102871","DOIUrl":"10.1016/j.sbi.2024.102871","url":null,"abstract":"<div><p>By incorporating full flexibility and enabling the quantification of crucial parameters such as binding free energies and residence times, methods for investigating protein-ligand binding and unbinding via molecular dynamics provide details on the involved mechanisms at the molecular level. While these advancements hold promise for impacting drug discovery, a notable drawback persists: their relatively time-consuming nature limits throughput. Herein, we survey recent implementations which, employing a blend of enhanced sampling techniques, a clever choice of collective variables, and often machine learning, strive to enhance the efficiency of new and previously reported methods without compromising accuracy. Particularly noteworthy is the validation of these methods that was often performed on systems mirroring real-world drug discovery scenarios.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"87 ","pages":"Article 102871"},"PeriodicalIF":6.1,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24000988/pdfft?md5=7c9ba0c1da68f50382108389cb8707f1&pid=1-s2.0-S0959440X24000988-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455755","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}
The expansion of the chemical space to tangible libraries containing billions of synthesizable molecules opens exciting opportunities for drug discovery, but also challenges the power of computer-aided drug design to prioritize the best candidates. This directly hits quantum mechanics (QM) methods, which provide chemically accurate properties, but subject to small-sized systems. Preserving accuracy while optimizing the computational cost is at the heart of many efforts to develop high-quality, efficient QM-based strategies, reflected in refined algorithms and computational approaches. The design of QM-tailored physics-based force fields and the coupling of QM with machine learning, in conjunction with the computing performance of supercomputing resources, will enhance the ability to use these methods in drug discovery. The challenge is formidable, but we will undoubtedly see impressive advances that will define a new era.
{"title":"Quantum mechanical-based strategies in drug discovery: Finding the pace to new challenges in drug design","authors":"Tiziana Ginex , Javier Vázquez , Carolina Estarellas , F.Javier Luque","doi":"10.1016/j.sbi.2024.102870","DOIUrl":"https://doi.org/10.1016/j.sbi.2024.102870","url":null,"abstract":"<div><p>The expansion of the chemical space to tangible libraries containing billions of synthesizable molecules opens exciting opportunities for drug discovery, but also challenges the power of computer-aided drug design to prioritize the best candidates. This directly hits quantum mechanics (QM) methods, which provide chemically accurate properties, but subject to small-sized systems. Preserving accuracy while optimizing the computational cost is at the heart of many efforts to develop high-quality, efficient QM-based strategies, reflected in refined algorithms and computational approaches. The design of QM-tailored physics-based force fields and the coupling of QM with machine learning, in conjunction with the computing performance of supercomputing resources, will enhance the ability to use these methods in drug discovery. The challenge is formidable, but we will undoubtedly see impressive advances that will define a new era.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"87 ","pages":"Article 102870"},"PeriodicalIF":6.1,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24000976/pdfft?md5=f828d7ecdbd34fd28c30ce96229060ef&pid=1-s2.0-S0959440X24000976-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444643","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}
Pub Date : 2024-06-22DOI: 10.1016/j.sbi.2024.102866
Shuo Han , Ling-Ling Chen
The nucleolus functions as a multi-layered regulatory hub for ribosomal RNA (rRNA) biogenesis and ribosome assembly. Long noncoding RNAs (lncRNAs) in the nucleolus, originated from transcription by different RNA polymerases, have emerged as critical players in not only fine-tuning rRNA transcription and processing, but also shaping the organization of the multi-phase nucleolar condensate. Here, we review the diverse molecular mechanisms by which functional lncRNAs operate in the nucleolus, as well as their profound implications in a variety of biological processes. We also highlight the development of emerging molecular tools for characterizing and manipulating RNA function in living cells, and how application of such tools in the nucleolus might enable the discovery of additional insights and potential therapeutic strategies.
{"title":"Long non-coding RNAs in the nucleolus: Biogenesis, regulation, and function","authors":"Shuo Han , Ling-Ling Chen","doi":"10.1016/j.sbi.2024.102866","DOIUrl":"https://doi.org/10.1016/j.sbi.2024.102866","url":null,"abstract":"<div><p>The nucleolus functions as a multi-layered regulatory hub for ribosomal RNA (rRNA) biogenesis and ribosome assembly. Long noncoding RNAs (lncRNAs) in the nucleolus, originated from transcription by different RNA polymerases, have emerged as critical players in not only fine-tuning rRNA transcription and processing, but also shaping the organization of the multi-phase nucleolar condensate. Here, we review the diverse molecular mechanisms by which functional lncRNAs operate in the nucleolus, as well as their profound implications in a variety of biological processes. We also highlight the development of emerging molecular tools for characterizing and manipulating RNA function in living cells, and how application of such tools in the nucleolus might enable the discovery of additional insights and potential therapeutic strategies.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"87 ","pages":"Article 102866"},"PeriodicalIF":6.1,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438566","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}
Pub Date : 2024-06-20DOI: 10.1016/j.sbi.2024.102865
Sarah Nemsick , Anders S. Hansen
Approximately 11% of human genes are transcribed by a bidirectional promoter (BDP), defined as two genes with <1 kb between their transcription start sites. Despite their evolutionary conservation and enrichment for housekeeping genes and oncogenes, the regulatory role of BDPs remains unclear. BDPs have been suggested to facilitate gene coregulation and/or decrease expression noise. This review discusses these potential regulatory functions through the context of six prospective underlying mechanistic models: a single nucleosome free region, shared transcription factor/regulator binding, cooperative negative supercoiling, bimodal histone marks, joint activation by enhancer(s), and RNA-mediated recruitment of regulators. These molecular mechanisms may act independently and/or cooperatively to facilitate the coregulation and/or decreased expression noise predicted of BDPs.
{"title":"Molecular models of bidirectional promoter regulation","authors":"Sarah Nemsick , Anders S. Hansen","doi":"10.1016/j.sbi.2024.102865","DOIUrl":"https://doi.org/10.1016/j.sbi.2024.102865","url":null,"abstract":"<div><p>Approximately 11% of human genes are transcribed by a bidirectional promoter (BDP), defined as two genes with <1 kb between their transcription start sites. Despite their evolutionary conservation and enrichment for housekeeping genes and oncogenes, the regulatory role of BDPs remains unclear. BDPs have been suggested to facilitate gene coregulation and/or decrease expression noise. This review discusses these potential regulatory functions through the context of six prospective underlying mechanistic models: a single nucleosome free region, shared transcription factor/regulator binding, cooperative negative supercoiling, bimodal histone marks, joint activation by enhancer(s), and RNA-mediated recruitment of regulators. These molecular mechanisms may act independently and/or cooperatively to facilitate the coregulation and/or decreased expression noise predicted of BDPs.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"87 ","pages":"Article 102865"},"PeriodicalIF":6.1,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434647","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}
Pub Date : 2024-06-19DOI: 10.1016/j.sbi.2024.102864
Alex J. Noble, Alex de Marco
Cryogenic-focused ion beam (cryo-FIB) instruments became essential for high-resolution imaging in cryo-preserved cells and tissues. Cryo-FIBs use accelerated ions to thin samples that would otherwise be too thick for cryo-electron microscopy (cryo-EM). This allows visualizing cellular ultrastructures in near-native frozen hydrated states. This review describes the current state-of-the-art capabilities of cryo-FIB technology and its applications in structural cell and tissue biology. We discuss recent advances in instrumentation, imaging modalities, automation, sample preparation protocols, and targeting techniques. We outline remaining challenges and future directions to make cryo-FIB more precise, enable higher throughput, and be widely accessible. Further improvements in targeting, efficiency, robust sample preparation, emerging ion sources, automation, and downstream electron tomography have the potential to reveal intricate molecular architectures across length scales inside cells and tissues. Cryo-FIB is poised to become an indispensable tool for preparing native biological systems in situ for high-resolution 3D structural analysis.
{"title":"Cryo-focused ion beam for in situ structural biology: State of the art, challenges, and perspectives","authors":"Alex J. Noble, Alex de Marco","doi":"10.1016/j.sbi.2024.102864","DOIUrl":"https://doi.org/10.1016/j.sbi.2024.102864","url":null,"abstract":"<div><p>Cryogenic-focused ion beam (cryo-FIB) instruments became essential for high-resolution imaging in cryo-preserved cells and tissues. Cryo-FIBs use accelerated ions to thin samples that would otherwise be too thick for cryo-electron microscopy (cryo-EM). This allows visualizing cellular ultrastructures in near-native frozen hydrated states. This review describes the current state-of-the-art capabilities of cryo-FIB technology and its applications in structural cell and tissue biology. We discuss recent advances in instrumentation, imaging modalities, automation, sample preparation protocols, and targeting techniques. We outline remaining challenges and future directions to make cryo-FIB more precise, enable higher throughput, and be widely accessible. Further improvements in targeting, efficiency, robust sample preparation, emerging ion sources, automation, and downstream electron tomography have the potential to reveal intricate molecular architectures across length scales inside cells and tissues. Cryo-FIB is poised to become an indispensable tool for preparing native biological systems in situ for high-resolution 3D structural analysis.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"87 ","pages":"Article 102864"},"PeriodicalIF":6.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24000915/pdfft?md5=facf3fbca25e633e212221fe7b841068&pid=1-s2.0-S0959440X24000915-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141429118","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}
Pub Date : 2024-06-17DOI: 10.1016/j.sbi.2024.102861
Abigail J.I. Watson , Alberto Bartesaghi
Cryogenic electron tomography (cryo-ET), a method that enables the viewing of biomolecules in near-native environments at high resolution, is rising in accessibility and applicability. Over the past several years, once slow sample preparation and data collection procedures have seen innovations which enable rapid collection of the large datasets required for attaining high resolution structures. Increased data availability has provided a driving force for exciting improvements in cryo-ET data processing methodologies throughout the entire processing pipeline and the development of accessible graphical user interfaces (GUIs) that enable individuals inexperienced in computational fields to convert raw tilt series into 3D structures. These advances in data processing are enabling cryo-ET to attain higher resolution and extending its applicability to more complex samples.
{"title":"Advances in cryo-ET data processing: meeting the demands of visual proteomics","authors":"Abigail J.I. Watson , Alberto Bartesaghi","doi":"10.1016/j.sbi.2024.102861","DOIUrl":"10.1016/j.sbi.2024.102861","url":null,"abstract":"<div><p>Cryogenic electron tomography (cryo-ET), a method that enables the viewing of biomolecules in near-native environments at high resolution, is rising in accessibility and applicability. Over the past several years, once slow sample preparation and data collection procedures have seen innovations which enable rapid collection of the large datasets required for attaining high resolution structures. Increased data availability has provided a driving force for exciting improvements in cryo-ET data processing methodologies throughout the entire processing pipeline and the development of accessible graphical user interfaces (GUIs) that enable individuals inexperienced in computational fields to convert raw tilt series into 3D structures. These advances in data processing are enabling cryo-ET to attain higher resolution and extending its applicability to more complex samples.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"87 ","pages":"Article 102861"},"PeriodicalIF":6.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24000885/pdfft?md5=9f902b53cfee390e3b02499c26d98828&pid=1-s2.0-S0959440X24000885-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418294","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}
Pub Date : 2024-06-17DOI: 10.1016/j.sbi.2024.102867
Rebecca K. Stephens, Yekaterina A. Miroshnikova
Cell fate changes require rewiring of transcriptional programs to generate functionally specialized cell states. Reconfiguration of transcriptional networks requires overcoming epigenetic barriers imposed by silenced heterochromatin in order to activate lineage-specific genes. Further, cell fate decisions are made in a tissue-specific context, where cells are physically linked to each other as well as to the connective tissue environment. Here, cells are continuously exposed to a multitude of mechanical forces emanating from cellular dynamics in their local microenvironments, for example through cell movements, cell divisions, tissue contractions, or fluid flow. Through their ability to deform cellular structures and activate receptors, mechanical forces can be sensed at the plasma membrane, but also at the nuclear periphery through direct or cytoskeleton-mediated deformation of the nuclear envelope. This deformation and the associated signaling is capable of triggering changes in the mechanical state of the nuclear membranes, the organization and rigidity of the underlying nuclear lamina, compaction state of chromatin, and ultimately transcription. This review focuses on the role of nuclear architecture, particularly the nuclear lamina-chromatin interface, and its mechanical regulation in cell fate decisions as well as its physiological role in development and cellular reprogramming.
{"title":"Nuclear periphery and its mechanical regulation in cell fate transitions","authors":"Rebecca K. Stephens, Yekaterina A. Miroshnikova","doi":"10.1016/j.sbi.2024.102867","DOIUrl":"10.1016/j.sbi.2024.102867","url":null,"abstract":"<div><p>Cell fate changes require rewiring of transcriptional programs to generate functionally specialized cell states. Reconfiguration of transcriptional networks requires overcoming epigenetic barriers imposed by silenced heterochromatin in order to activate lineage-specific genes. Further, cell fate decisions are made in a tissue-specific context, where cells are physically linked to each other as well as to the connective tissue environment. Here, cells are continuously exposed to a multitude of mechanical forces emanating from cellular dynamics in their local microenvironments, for example through cell movements, cell divisions, tissue contractions, or fluid flow. Through their ability to deform cellular structures and activate receptors, mechanical forces can be sensed at the plasma membrane, but also at the nuclear periphery through direct or cytoskeleton-mediated deformation of the nuclear envelope. This deformation and the associated signaling is capable of triggering changes in the mechanical state of the nuclear membranes, the organization and rigidity of the underlying nuclear lamina, compaction state of chromatin, and ultimately transcription. This review focuses on the role of nuclear architecture, particularly the nuclear lamina-chromatin interface, and its mechanical regulation in cell fate decisions as well as its physiological role in development and cellular reprogramming.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"87 ","pages":"Article 102867"},"PeriodicalIF":6.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418295","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}
Pub Date : 2024-06-15DOI: 10.1016/j.sbi.2024.102863
Elizabeth Marie Irvin , Hong Wang
Defining the molecular mechanisms by which genome maintenance proteins dynamically associate with and process DNA is essential to understand the potential avenues by which these stabilizing mechanisms are disrupted. Single-molecule fluorescence imaging (SMFI) of protein dynamics on extended DNA has greatly expanded our ability to accomplish this, as it captures singular biomolecular interactions – in all their complexity and diversity – without relying on ensemble-averaging of bulk protein activity as most traditional biochemical techniques must do. In this review, we discuss how SMFI studies with extended DNA have substantially contributed to genome stability research over the past two years.
要了解这些稳定机制被破坏的潜在途径,就必须确定基因组维护蛋白与 DNA 动态关联和处理 DNA 的分子机制。对扩展 DNA 上蛋白质动态的单分子荧光成像(SMFI)极大地拓展了我们实现这一目标的能力,因为它能捕捉单个生物分子的相互作用--其复杂性和多样性--而不像大多数传统生化技术那样必须依赖于大量蛋白质活性的集合平均。在这篇综述中,我们将讨论在过去两年中,利用扩展 DNA 进行的 SMFI 研究是如何为基因组稳定性研究做出重大贡献的。
{"title":"Single-molecule fluorescence imaging of DNA maintenance protein binding dynamics and activities on extended DNA","authors":"Elizabeth Marie Irvin , Hong Wang","doi":"10.1016/j.sbi.2024.102863","DOIUrl":"https://doi.org/10.1016/j.sbi.2024.102863","url":null,"abstract":"<div><p>Defining the molecular mechanisms by which genome maintenance proteins dynamically associate with and process DNA is essential to understand the potential avenues by which these stabilizing mechanisms are disrupted. Single-molecule fluorescence imaging (SMFI) of protein dynamics on extended DNA has greatly expanded our ability to accomplish this, as it captures singular biomolecular interactions – in all their complexity and diversity – without relying on ensemble-averaging of bulk protein activity as most traditional biochemical techniques must do. In this review, we discuss how SMFI studies with extended DNA have substantially contributed to genome stability research over the past two years.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"87 ","pages":"Article 102863"},"PeriodicalIF":6.8,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328777","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}
Pub Date : 2024-06-14DOI: 10.1016/j.sbi.2024.102868
Shuai Li, Charan Vemuri, Chongyi Chen
Double helical DNA winds around nucleosomes, forming a beads-on-a-string array that further contributes to the formation of high-order chromatin structures. The regulatory components of the chromatin, interacting intricately with DNA, often exploit the topological tension inherent in the DNA molecule. Recent findings shed light on, and simultaneously complicate, the multifaceted roles of DNA topology (also known as DNA supercoiling) in various aspects of chromatin regulation. Different studies may emphasize the dynamics of DNA topological tension across different scales, interacting with diverse chromatin factors such as nucleosomes, nucleic acid motors that propel DNA-tracking processes, and DNA topoisomerases. In this review, we consolidate recent studies and establish connections between distinct scientific discoveries, advancing our current understanding of chromatin regulation mediated by the supercoiling tension of the double helix. Additionally, we explore the implications of DNA topology and DNA topoisomerases in human diseases, along with their potential applications in therapeutic interventions.
双螺旋 DNA 缠绕在核小体上,形成串珠阵列,进一步促进了高阶染色质结构的形成。染色质中的调控成分与 DNA 相互作用,经常利用 DNA 分子固有的拓扑张力。最近的发现揭示了 DNA 拓扑学(也称为 DNA 超卷曲)在染色质调控各方面的多方面作用,同时也使其变得更加复杂。不同的研究可能会强调 DNA 拓扑张力在不同尺度上的动态变化,并与核小体、推动 DNA 跟踪过程的核酸马达和 DNA 拓扑异构酶等多种染色质因子相互作用。在这篇综述中,我们整合了最近的研究,并在不同的科学发现之间建立了联系,从而推进了我们目前对由双螺旋超卷曲张力介导的染色质调控的理解。此外,我们还探讨了DNA拓扑学和DNA拓扑异构酶对人类疾病的影响,以及它们在治疗干预中的潜在应用。
{"title":"DNA topology: A central dynamic coordinator in chromatin regulation","authors":"Shuai Li, Charan Vemuri, Chongyi Chen","doi":"10.1016/j.sbi.2024.102868","DOIUrl":"https://doi.org/10.1016/j.sbi.2024.102868","url":null,"abstract":"<div><p>Double helical DNA winds around nucleosomes, forming a beads-on-a-string array that further contributes to the formation of high-order chromatin structures. The regulatory components of the chromatin, interacting intricately with DNA, often exploit the topological tension inherent in the DNA molecule. Recent findings shed light on, and simultaneously complicate, the multifaceted roles of DNA topology (also known as DNA supercoiling) in various aspects of chromatin regulation. Different studies may emphasize the dynamics of DNA topological tension across different scales, interacting with diverse chromatin factors such as nucleosomes, nucleic acid motors that propel DNA-tracking processes, and DNA topoisomerases. In this review, we consolidate recent studies and establish connections between distinct scientific discoveries, advancing our current understanding of chromatin regulation mediated by the supercoiling tension of the double helix. Additionally, we explore the implications of DNA topology and DNA topoisomerases in human diseases, along with their potential applications in therapeutic interventions.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"87 ","pages":"Article 102868"},"PeriodicalIF":6.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141323753","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}
Pub Date : 2024-06-12DOI: 10.1016/j.sbi.2024.102862
Tero Aittokallio, Evandro Fei Fang
{"title":"Editorial overview–Artificial intelligence methodologies in structural biology: Bridging the gap to medical applications","authors":"Tero Aittokallio, Evandro Fei Fang","doi":"10.1016/j.sbi.2024.102862","DOIUrl":"https://doi.org/10.1016/j.sbi.2024.102862","url":null,"abstract":"","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"87 ","pages":"Article 102862"},"PeriodicalIF":6.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308082","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}