Current opinion in structural biology最新文献

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Cryo-focused ion beam milling for cryo-electron tomography: Shaping the future of in situ structural biology 低温聚焦离子束铣削用于低温电子断层扫描：塑造原位结构生物学的未来

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-22 DOI: 10.1016/j.sbi.2025.103138

Sven Klumpe , Jürgen M. Plitzko

Cryo-focused ion beam instruments to produce cellular thin sections for subsequent imaging by cryo-electron tomography have become an integral part of the methodologies for in situ structural biology, enabling high-resolution imaging of biological structures in their native environment. The application of these instruments has opened windows into cells that allowed unprecedented insights into the ultrastructure of cells and more recently, small multicellular organisms and tissues. While great strides have been made in the characterization of cryo-FIB milling and the streamlining of workflows with these tools, many limitations and technical challenges remain to be resolved. Here, we discuss the technical and technological challenges ahead to continue the steep rise of biological discoveries by in-cell cryo-electron tomography to enable cellular structural biology in the multicellular context.

低温聚焦离子束仪器为随后的低温电子断层成像生产细胞薄切片，已经成为原位结构生物学方法的一个组成部分，使生物结构在其原生环境中的高分辨率成像成为可能。这些仪器的应用为研究细胞打开了一扇窗，使我们能够前所未有地深入了解细胞的超微结构，以及最近的小型多细胞生物和组织。虽然在低温fib铣削表征和使用这些工具简化工作流程方面取得了很大进展，但仍有许多限制和技术挑战有待解决。在这里，我们讨论了未来的技术和技术挑战，以继续通过细胞内低温电子断层扫描来实现多细胞环境下的细胞结构生物学的生物学发现。

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Role of RNA in genome folding: It's all about affinity RNA在基因组折叠中的作用：这与亲和力有关

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-20 DOI: 10.1016/j.sbi.2025.103136

Rafal Czapiewski, Nick Gilbert

In mammalian cells, RNA species make up ∼10% of chromatin by mass and play a structural role in the nucleus by acting as scaffolds and influencing genome organisation. Although many proteins bind nuclear RNAs, these interactions are often non-specific, making it challenging to define RNA's role in genome folding. Nonetheless, a clearer picture is emerging. Some RNAs, like NEAT1 and MALAT1, have high affinity for specific RNA-binding proteins and form the basis for nuclear bodies. In contrast, many nuclear proteins bind RNA weakly, resulting in numerous low-affinity interactions. We propose that these interactions generate a complex RNA-protein network with dynamic, gel-like properties that modulate chromatin folding and transcription factor mobility. This suggests an exciting feedback mechanism in which newly transcribed RNA contributes directly to shaping chromatin architecture.

在哺乳动物细胞中，RNA种类占染色质质量的约10%，并通过充当支架和影响基因组组织在细胞核中发挥结构作用。尽管许多蛋白质结合核RNA，但这些相互作用通常是非特异性的，这使得定义RNA在基因组折叠中的作用具有挑战性。尽管如此，一幅更清晰的图景正在浮现。一些rna，如NEAT1和MALAT1，对特定的rna结合蛋白具有高亲和力，是核体的基础。相比之下，许多核蛋白与RNA结合较弱，导致许多低亲和力相互作用。我们提出，这些相互作用产生了一个复杂的rna -蛋白网络，具有动态的凝胶样特性，可以调节染色质折叠和转录因子的迁移。这表明了一种令人兴奋的反馈机制，其中新转录的RNA直接有助于形成染色质结构。

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Functional sub-states link conformational landscapes and protein evolution 功能亚态连接构象景观和蛋白质进化

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-16 DOI: 10.1016/j.sbi.2025.103134

Morito Sakuma , Karol Buda , H. Adrian Bunzel , Christopher Frøhlich , Nobuhiko Tokuriki

The intrinsic conformational flexibility of proteins creates structural heterogeneity, giving rise to conformational ensembles within the energy landscape. When conformational ensembles harbor distinct functional sub-states, mutations can reshape the conformational landscape, thereby altering the distribution of functional sub-states and driving the evolution of novel functions. In this review, we provide a conceptual framework that elucidates the importance of functional sub-states and how evolution can select them. We highlight key studies that have uncovered functional sub-states and discuss recent insights into the transitions of functional sub-states during evolutionary trajectories. Finally, we outline critical techniques for studying functional sub-states, address the challenges faced in analyzing these sub-states, and explore future advancements in the field of protein evolution.

蛋白质固有的构象灵活性创造了结构的异质性，在能量景观中产生了构象集成。当构象集合体包含不同的功能亚态时，突变可以重塑构象景观，从而改变功能亚态的分布并驱动新功能的进化。在这篇综述中，我们提供了一个概念框架，阐明了功能子状态的重要性以及进化如何选择它们。我们重点介绍了发现功能亚状态的关键研究，并讨论了进化轨迹中功能亚状态转变的最新见解。最后，我们概述了研究功能亚状态的关键技术，解决了分析这些亚状态所面临的挑战，并探讨了蛋白质进化领域的未来进展。

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Modeling flexible RNA 3D structures and RNA-protein complexes 建模柔性RNA三维结构和RNA-蛋白复合物

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-16 DOI: 10.1016/j.sbi.2025.103137

Rui João Loureiro, Satyabrata Maiti, Kuntal Mondal, Sunandan Mukherjee, Janusz M. Bujnicki

RNA and RNA–protein (RNP) complexes are central to many cellular processes, but the determination of their structures remains challenging due to RNA flexibility and interaction diversity. This review highlights recent computational advances, particularly from the past two years, in predicting and analyzing RNA and RNP structures. We discuss template-based modeling, docking, molecular simulations, and deep learning approaches, with an emphasis on emerging hybrid methods that integrate these strategies. Special attention is given to tools for modeling conformational heterogeneity, folding pathways, and dynamic binding. We also outline machine learning and simulation techniques for ensemble prediction and explore future directions including quantum-enhanced modeling. Together, these developments are enabling more accurate and scalable modeling of both the static and dynamic aspects of RNA and RNP complexes.

RNA和RNA -蛋白（RNP）复合物是许多细胞过程的核心，但由于RNA的灵活性和相互作用的多样性，确定其结构仍然具有挑战性。这篇综述强调了最近的计算进展，特别是过去两年，在预测和分析RNA和RNP结构方面。我们讨论了基于模板的建模、对接、分子模拟和深度学习方法，重点介绍了整合这些策略的新兴混合方法。特别注意的是建模的工具构象异质性，折叠途径，和动态结合。我们还概述了集成预测的机器学习和模拟技术，并探索了未来的方向，包括量子增强建模。总之，这些发展使RNA和RNP复合物的静态和动态方面的建模更加准确和可扩展。

引用次数: 0

Advances in Protein-RNA aptamer recognition and modeling: Current trends and future perspectives 蛋白质- rna适体识别和建模的进展：当前趋势和未来展望

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-14 DOI: 10.1016/j.sbi.2025.103133

Liming Qiu , Xiaoqin Zou

RNA aptamers possess a remarkable ability to selectively target a diverse spectrum of biomolecules with exceptional affinity and specificity. Their distinctive physical and chemical attributes have driven extensive research into their therapeutic, diagnostic, and analytical applications. However, experimental approaches alone are insufficient to meet the growing demand. As a result, accurate and efficient computational methods are playing an increasingly vital role in RNA aptamer sequence design and structural modeling. Recent breakthroughs in biomolecular structure prediction, particularly through deep learning, have further spurred the development of innovative algorithms. In this review, we summarize current computational models for RNA aptamer structure prediction and design, highlighting recent advances in the field.

RNA适配体具有非凡的亲和力和特异性，能够选择性地靶向多种生物分子。它们独特的物理和化学特性推动了对其治疗、诊断和分析应用的广泛研究。然而，仅靠实验方法不足以满足日益增长的需求。因此，精确、高效的计算方法在RNA适体序列设计和结构建模中发挥着越来越重要的作用。最近在生物分子结构预测方面的突破，特别是通过深度学习，进一步刺激了创新算法的发展。在这篇综述中，我们总结了目前用于RNA适体结构预测和设计的计算模型，重点介绍了该领域的最新进展。

引用次数: 0

Generative AI techniques for conformational diversity and evolutionary adaptation of proteins 蛋白质构象多样性和进化适应的生成人工智能技术

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-14 DOI: 10.1016/j.sbi.2025.103135

Alfie-Louise R. Brownless , Dariia Yehorova , Colin L. Welsh , Shina Caroline Lynn Kamerlin

The advent of AlphaFold and consumer large language models have elicited unprecedented development of artificial intelligence (AI). AI has had substantial impact in every area of research, including in molecular biology. This is principally in thanks to contributions to the Protein Data Bank and various genome sequence databases, providing an astronomical amount of data for model training. These databases contain evolutionary information explicitly and implicitly, allowing accurate predictions and deep insights into biological questions. Here, we describe recent state-of-the-art applications of AI that exploit evolutionary relationships. This includes structure prediction and design, conformational ensemble generation, and functional site identification. We present a brief snapshot of AI usage in studying protein structure and dynamics, a field that is advancing at breakneck speed.

AlphaFold和消费级大语言模型的出现，引发了人工智能（AI）的空前发展。人工智能在包括分子生物学在内的每个研究领域都产生了重大影响。这主要是由于对蛋白质数据库和各种基因组序列数据库的贡献，为模型训练提供了天文数字的数据量。这些数据库明确地或隐含地包含了进化信息，允许对生物学问题进行准确的预测和深入的了解。在这里，我们描述了利用进化关系的人工智能的最新应用。这包括结构预测和设计、构象集合生成和功能位点识别。我们简要介绍了人工智能在研究蛋白质结构和动力学方面的应用，这一领域正在以惊人的速度发展。

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Global dynamics behind enzyme catalysis, evolution, and design 酶催化、进化和设计背后的全球动力学

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-12 DOI: 10.1016/j.sbi.2025.103131

Burcu Aykac Fas , Zeynep Erge Akbas Buz , Turkan Haliloglu

Enzymes are inherently dynamic entities, with their functions intricately governed by the interplay between conformational dynamics - ranging from local residue fluctuations to global motions - and biochemical activity. Deciphering how such dynamics coordinate higher-order cooperativity across multiple timescales to drive catalysis remains a fundamental challenge. This mini-review highlights the role of large-scale, collective motions involving domain-level displacements and hinge-based rearrangements, which not only facilitate substrate recognition, transformation, and release, but also emerge from and propagate through multidirectional allosteric interactions. Such dynamic mechanochemical coupling reflects evolutionary memory and provides a blueprint for enzyme design innovations.

酶本质上是动态的实体，其功能受到构象动力学（从局部残留波动到全局运动）和生化活性之间相互作用的复杂控制。破译这种动力学如何在多个时间尺度上协调高阶协同性来驱动催化仍然是一个根本性的挑战。这篇综述强调了涉及域水平位移和基于铰链的重排的大规模集体运动的作用，这些运动不仅促进了底物的识别、转化和释放，而且还通过多向变构相互作用产生和传播。这种动态的机械化学耦合反映了进化记忆，并为酶设计创新提供了蓝图。

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Advances in native cell membrane nanoparticles system 天然细胞膜纳米颗粒体系的研究进展

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-06 DOI: 10.1016/j.sbi.2025.103130

Weihua Qiu , Youzhong Guo

The native cell membrane nanoparticles (NCMN) system utilizes membrane-active polymers specifically designed and optimized to extract and stabilize membrane proteins in the form of NCMN particlesfor biochemical and biophysical characterization. The NCMN system is a genuine and advanced detergent-free approach inspired by the membrane activity of the styrene–maleic acid copolymers (SMA), distinguishing it from the nanodisc technology, Salipro technology, and Peptidisc technology. This review introduces the current advancements in the NCMN system, including the development of NCMN polymers, the application of the NCMN system for single-particle cryo-EM analysis, and the functional characterization of membrane proteins.

天然细胞膜纳米颗粒（NCMN）系统利用专门设计和优化的膜活性聚合物，以NCMN颗粒的形式提取和稳定膜蛋白，用于生化和生物物理表征。NCMN系统是一种真正先进的无洗涤剂方法，其灵感来自于苯乙烯-马来酸共聚物（SMA）的膜活性，将其与纳米盘技术、Salipro技术和肽盘技术区分开来。本文介绍了NCMN系统的最新进展，包括NCMN聚合物的发展，NCMN系统在单颗粒低温电镜分析中的应用，以及膜蛋白的功能表征。

引用次数: 0

HIV-1 gp160 in nanodiscs: Unravelling structures and guiding vaccine design 纳米圆盘中的HIV-1 gp160：揭示结构和指导疫苗设计

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-05 DOI: 10.1016/j.sbi.2025.103122

Nancy M. Elbaz, Mahmoud L. Nasr

The stabilization of HIV-1 gp160 trimers (Env) within phospholipid bilayer nanodiscs has provided critical structural insights into the membrane-proximal external region (MPER) and the broader dynamics of gp160. Cryo-EM and molecular simulations reveal that the membrane context preserves the MPER architecture and captures spontaneous trimer asymmetry, as well as ectodomain tilting. These dynamic properties expose vulnerable epitopes that are targeted by broadly neutralizing antibodies (bnAbs). Studies using nanodiscs have highlighted how interactions with the membrane affect the structure of gp160, the accessibility of epitopes, and the mechanisms of neutralization, providing important insights for immunogen design. Unlike soluble SOSIP and IDL constructs, full-length nanodisc-embedded gp160 maintains its native stability, flexibility, and the complete set of neutralization epitopes, suggesting that membrane-mimicking platforms are essential for the rational design of next-generation HIV vaccines targeting conserved regions, such as the MPER.

磷脂双层纳米圆盘内HIV-1 gp160三聚体（Env）的稳定为膜近端外区（MPER）和gp160更广泛的动力学提供了关键的结构见解。低温电镜和分子模拟表明，膜环境保留了MPER结构，并捕获了自发的三聚体不对称，以及外畴倾斜。这些动态特性暴露了易受攻击的表位，这些表位是广泛中和抗体（bnAbs）的目标。利用纳米片的研究强调了与膜的相互作用如何影响gp160的结构、表位的可及性和中和机制，为免疫原设计提供了重要的见解。与可溶性SOSIP和IDL构建物不同，全长纳米圆盘嵌入的gp160保持了其固有的稳定性、灵活性和完整的中和表位，这表明膜模拟平台对于合理设计针对保守区域（如MPER）的下一代HIV疫苗至关重要。

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Frustration, dynamics, and catalysis 挫折，动力和催化

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology

Pub Date : 2025-08-05 DOI: 10.1016/j.sbi.2025.103127

R. Gonzalo Parra , Diego U. Ferreiro

The controlled dissipation of chemical potentials is the fundamental way cells make a living. Enzyme-mediated catalysis allows the various transformations to proceed at biologically relevant rates with remarkable precision and efficiency. Theory, experiments, and computational studies coincide to show that local frustration is a useful concept to relate protein dynamics with catalytic power. Local frustration gives rise to the asperities of the energy landscapes that can harness the thermal fluctuations to guide the functional protein motions. We review here recent advances into these relationships from various fields of protein science. The biologically relevant dynamics is tuned by the evolution of protein sequences that modulate local frustration patterns to near-optimal values.

控制化学势的耗散是细胞生存的基本方式。酶介导的催化使各种转化以生物学相关的速度进行，具有显著的精度和效率。理论、实验和计算研究一致表明，局部挫折是一个有用的概念，将蛋白质动力学与催化力联系起来。局部挫折导致能量景观的凹凸不平，可以利用热波动来指导功能性蛋白质的运动。在此，我们回顾了蛋白质科学各个领域对这些关系的最新进展。生物相关的动态是通过蛋白质序列的进化来调节局部挫折模式到接近最佳值。

引用次数: 0

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