Journal of Molecular Biology最新文献_第2页

memerna: Sparse RNA folding including coaxial stacking memerna：稀疏 RNA 折叠（包括同轴堆积）。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-02-01 DOI: 10.1016/j.jmb.2024.168819

Eliot Courtney , Amitava Datta , David H. Mathews , Max Ward

{"title":"memerna: Sparse RNA folding including coaxial stacking","authors":"Eliot Courtney , Amitava Datta , David H. Mathews , Max Ward","doi":"10.1016/j.jmb.2024.168819","DOIUrl":"10.1016/j.jmb.2024.168819","url":null,"abstract":"<div><div>Determining RNA secondary structure is a core problem in computational biology. Fast algorithms for predicting secondary structure are fundamental to this task. We describe a modified formulation of the Zuker-Stiegler algorithm with coaxial stacking, a stabilising interaction in which the ends of helices in multi-loops are stacked. In particular, optimal coaxial stacking is computed as part of the dynamic programming state, rather than in an inner loop. We introduce a new notion of sparsity, which we call <em>replaceability</em>. Replaceability is a more general condition and applicable in more places than the <em>triangle inequality</em> that is used by previous sparse folding methods. We also introduce non-monotonic candidate lists as an additional sparsification tool. Existing usages of the triangle inequality for sparsification can be thought of as an application of both replaceability and monotonicity together. The modified recurrences along with replaceability allows sparsification to be applied to coaxial stacking as well, which increases the speed of the algorithm. We implemented this algorithm in software we call <em>memerna</em>, which we show to have the fastest exact (non–heuristic) implementation of RNA folding under the complete Turner 2004 model with coaxial stacking, out of several popular RNA folding tools supporting coaxial stacking. We also introduce a new notation for secondary structure which includes coaxial stacking, terminal mismatches, and dangles (CTDs) information. The memerna package 0.1 release is available at https://github.com/Edgeworth/memerna/tree/release/0.1.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 3","pages":"Article 168819"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454993","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

AllohubPy: Detecting allosteric signals through an information-theoretic approach.

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-02-01 DOI: 10.1016/j.jmb.2025.168969

Oriol Gracia Carmona, Jens Kleinjung, Dimitrios Anastasiou, Chris Oostenbrink, Franca Fraternali

{"title":"AllohubPy: Detecting allosteric signals through an information-theoretic approach.","authors":"Oriol Gracia Carmona, Jens Kleinjung, Dimitrios Anastasiou, Chris Oostenbrink, Franca Fraternali","doi":"10.1016/j.jmb.2025.168969","DOIUrl":"https://doi.org/10.1016/j.jmb.2025.168969","url":null,"abstract":"<p><p>Allosteric regulation is crucial for biological processes like signal transduction, transcriptional regulation, and metabolism, yet the mechanisms and macromolecular properties that govern it are still not well understood. Several methods have been developed over the years to study allosterism through different angles. Among the possible ways to study allosterism, information-theoretic approaches, like AlloHubMat or GSAtools, can be particularly effective due to their use of robust statistics and the possibility to be combined with graph analysis. These methods capture local conformational changes associated with global motions from molecular dynamics simulations through the use of a Structural Alphabet, which simplifies the complexity of the Cartesian space by reducing the dimensionality down to a string of encoded fragments, representing sets of internal coordinates that still capture the overall conformation changes. In this work, we present \"AllohubPy,\" an improved and standardized methodology of AlloHubMat and GSAtools coded in Python. We analyse the performance, limitations and sampling requirements of AllohubPy by using extensive molecular dynamics simulations of model allosteric systems and apply convergence analysis techniques to estimate result reliability. Additionally, we expand the methodology to use different dimensionality reduction Structural Alphabets, such as the 3DI alphabet, and integrate Protein Language Models (PLMs) to refine allosteric hub communication detection by monitoring the detected evolutionary constraints. Overall, AllohubPy expands its preceding methods and simplifies the use and reliability of the method to effectively capture dynamic allosteric motions and residue pathways. AllohubPy is freely available on GitHub (https://github.com/Fraternalilab/AlloHubPy) as a package and as a Jupyter Notebook.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168969"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121924","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 Dynamics of Rho GTPases Rho GTPases的结构动力学。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-02-01 DOI: 10.1016/j.jmb.2024.168919

Yuan Lin , Yi Zheng

引用次数: 0

Phosphorylation-Dependent Dispersion of the Response Regulator in Bacterial Chemotaxis 细菌趋化性中反应调节因子的磷酸化依赖分散。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-02-01 DOI: 10.1016/j.jmb.2024.168920

Shirui Ruan , Rui He , Yixin Liang, Rongjing Zhang, Junhua Yuan

引用次数: 0

rcsb-api: Python Toolkit for Streamlining Access to RCSB Protein Data Bank APIs.

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-29 DOI: 10.1016/j.jmb.2025.168970

Dennis W Piehl, Brinda Vallat, Ivana Truong, Habiba Morsy, Rusham Bhatt, Santiago Blaumann, Pratyoy Biswas, Yana Rose, Sebastian Bittrich, Jose M Duarte, Joan Segura, Chunxiao Bi, Douglas Myers-Turnbull, Brian P Hudson, Christine Zardecki, Stephen K Burley

{"title":"rcsb-api: Python Toolkit for Streamlining Access to RCSB Protein Data Bank APIs.","authors":"Dennis W Piehl, Brinda Vallat, Ivana Truong, Habiba Morsy, Rusham Bhatt, Santiago Blaumann, Pratyoy Biswas, Yana Rose, Sebastian Bittrich, Jose M Duarte, Joan Segura, Chunxiao Bi, Douglas Myers-Turnbull, Brian P Hudson, Christine Zardecki, Stephen K Burley","doi":"10.1016/j.jmb.2025.168970","DOIUrl":"https://doi.org/10.1016/j.jmb.2025.168970","url":null,"abstract":"<p><p>The Protein Data Bank (PDB) was founded in 1971 as the first open-access digital data resource in biology to serve as the single global archive for three-dimensional (3D) macromolecular structure data. Current PDB holdings exceed 230,000 experimentally determined structures of proteins, nucleic acids, viruses, and macromolecular machines. The RCSB Protein Data Bank RCSB.org research-focused web portal facilitates search, analyses, and visualization of every PDB structure along with more than one million Computed Structure Models from AlphaFold DB and the ModelArchive. It is powered by a set of publicly available Application Programming Interfaces (APIs) that both support RCSB.org users and provide programmatic access to PDB data. Given the breadth and levels of granularity encompassed in this rich data collection, efficiently accessing the information programmatically may be challenging for new users. RCSB PDB has developed a Python software package, rcsb-api, that facilitates easy and efficient use of RCSB PDB APIs within a Python environment. This software tool is designed to streamline access to the extensive corpus of data housed within the PDB, enabling researchers to search, retrieve, and analyze 3D biostructure data seamlessly. Its use will accelerate research in structural biology, molecular biology and biochemistry, drug discovery, and bioinformatics by providing more efficient tools for data integration and analysis. The new toolkit is available on GitHub (github.com/rcsb/py-rcsb-api) and published to the public Python package repository (PyPI) to foster wider usage and support basic and applied research in fundamental biology, biomedicine, and the energy sciences.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168970"},"PeriodicalIF":4.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078369","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

Caps-ac4C: An effective computational framework for identifying N4-acetylcytidine sites in human mRNA based on deep learning.

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-28 DOI: 10.1016/j.jmb.2025.168961

Lantian Yao, Peilin Xie, Danhong Dong, Yilin Guo, Jiahui Guan, Wenyang Zhang, Chia-Ru Chung, Zhihao Zhao, Ying-Chih Chiang, Tzong-Yi Lee

{"title":"Caps-ac4C: An effective computational framework for identifying N4-acetylcytidine sites in human mRNA based on deep learning.","authors":"Lantian Yao, Peilin Xie, Danhong Dong, Yilin Guo, Jiahui Guan, Wenyang Zhang, Chia-Ru Chung, Zhihao Zhao, Ying-Chih Chiang, Tzong-Yi Lee","doi":"10.1016/j.jmb.2025.168961","DOIUrl":"10.1016/j.jmb.2025.168961","url":null,"abstract":"<p><p>N4-acetylcytidine (ac4C) is a crucial post-transcriptional modification in human mRNA, involving the acetylation of the nitrogen atom at the fourth position of cytidine. This modification, catalyzed by N-acetyltransferases such as NAT10, is primarily found in mRNA's coding regions and enhances translation efficiency and mRNA stability. ac4C is closely associated with various diseases, including cancer. Therefore, accurately identifying ac4C in human mRNA is essential for gaining deeper insights into disease pathogenesis and provides potential pathways for the development of novel medical interventions. In silico methods for identifying ac4C are gaining increasing attention due to their cost-effectiveness, requiring minimal human and material resources. In this study, we propose an efficient and accurate computational framework, Caps-ac4C, for the precise detection of ac4C in human mRNA. Caps-ac4C utilizes chaos game representation to encode RNA sequences into \"images\" and employs capsule networks to learn global and local features from these RNA \"images\". Experimental results demonstrate that Caps-ac4C achieves state-of-the-art performance, achieving 95.47% accuracy and 0.912 MCC on the test set, surpassing the current best methods by 10.69% accuracy and 0.216 MCC. In summary, Caps-ac4C represents the most accurate tool for predicting ac4C sites in human mRNA, highlighting its significant contribution to RNA modification research. For user convenience, we developed a user-friendly web server, which can be accessed for free at:https://awi.cuhk.edu.cn/∼Caps-ac4C/index.php.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168961"},"PeriodicalIF":4.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063034","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

Predicting Metal-binding Proteins and Structures Through Integration of Evolutionary-scale and Physics-based Modeling.

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-27 DOI: 10.1016/j.jmb.2025.168962

Xin Dai, Max Henderson, Shinjae Yoo, Qun Liu

{"title":"Predicting Metal-binding Proteins and Structures Through Integration of Evolutionary-scale and Physics-based Modeling.","authors":"Xin Dai, Max Henderson, Shinjae Yoo, Qun Liu","doi":"10.1016/j.jmb.2025.168962","DOIUrl":"10.1016/j.jmb.2025.168962","url":null,"abstract":"<p><p>Metals are essential elements in all living organisms, binding to approximately 50% of proteins. They serve to stabilize proteins, catalyze reactions, regulate activities, and fulfill various physiological and pathological functions. While there have been many advancements in determining the structures of protein-metal complexes, numerous metal-binding proteins still need to be identified through computational methods and validated through experiments. To address this need, we have developed the ESMBind workflow, which combines evolutionary scale modeling (ESM) for metal-binding prediction and physics-based protein-metal modeling. Our approach utilizes the ESM-2 and ESM-IF models to predict metal-binding probability at the residue level. In addition, we have designed a metal-placement method and energy minimization technique to generate detailed 3D structures of protein-metal complexes. Our workflow outperforms other models in terms of residue and 3D-level predictions. To demonstrate its effectiveness, we applied the workflow to 142 uncharacterized fungal pathogen proteins and predicted metal-binding proteins involved in fungal infection and virulence.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168962"},"PeriodicalIF":4.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045190","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

Phase-separated Condensates in Autophagosome Formation and Autophagy Regulation.

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-27 DOI: 10.1016/j.jmb.2025.168964

Zheng Wang, Hong Zhang

{"title":"Phase-separated Condensates in Autophagosome Formation and Autophagy Regulation.","authors":"Zheng Wang, Hong Zhang","doi":"10.1016/j.jmb.2025.168964","DOIUrl":"10.1016/j.jmb.2025.168964","url":null,"abstract":"<p><p>Biomacromolecules partition into numerous types of biological condensates or membrane-less organelles via liquid-liquid phase separation (LLPS). Newly formed liquid-like condensates may further undergo phase transition to convert into other material states, such as gel or solid states. Different biological condensates possess distinct material properties to fulfil their physiological functions in diverse cellular pathways and processes. Phase separation and condensates are extensively involved in the autophagy pathway. The autophagosome formation sites in both yeast and multicellular organisms are assembled as phase-separated condensates. TORC1, one of the core regulators of the autophagy-lysosome pathway, is subject to nonconventional regulation by multiple biological condensates. TFEB, the master transcription factor of the autophagy-lysosome pathway, phase separates to assemble liquid-like condensates involved in transcription of autophagic and lysosomal genes. The behaviors and transcriptional activity of TFEB condensates are governed by their material properties, thus suggesting novel autophagy intervention strategies. The phase separation process and the resulting condensates are emerging therapeutic targets for autophagy-related diseases.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168964"},"PeriodicalIF":4.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063036","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

Evolution of Transcription Factor-containing Superfamilies in Eukaryotes

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-23 DOI: 10.1016/j.jmb.2025.168959

Akshara Dubey , Ganesh Muthu , Aswin Sai Narain Seshasayee

{"title":"Evolution of Transcription Factor-containing Superfamilies in Eukaryotes","authors":"Akshara Dubey , Ganesh Muthu , Aswin Sai Narain Seshasayee","doi":"10.1016/j.jmb.2025.168959","DOIUrl":"10.1016/j.jmb.2025.168959","url":null,"abstract":"<div><div>Regulation of gene expression helps determine various phenotypes in most cellular life forms. It is orchestrated at different levels and at the point of transcription initiation by transcription factors (TFs). TFs bind to DNA through domains that are evolutionarily related, by shared membership of the same superfamilies (TF-SFs), to those found in other nucleic acid binding and protein-binding functions (nTFs for non-TFs). Here we ask how TF DNA binding sequence families in eukaryotes have evolved in relation to their nTF relatives. TF numbers scale by power law with the total number of protein-coding genes differently in different clades, with fungi usually showing sub-linear powers whereas chordates show super-linear scaling. The LECA probably encoded a complex regulatory machinery with both TFs and nTFs, but with an excess of nTFs when compared to the relative distribution of TFs and nTFs in extant organisms. Losses drive the evolution of TFs and nTFs, with the possible exception of TFs in animals for some tree topologies. TFs are highly dynamic in evolution, showing higher gain and loss rates than nTFs in some TF-SFs though both are conserved to similar extents. Gains of TFs and nTFs are driven by the appearance of a large number of new sequence clusters in a small number of nodes, which determine the presence of as many as a third of extant TFs and nTFs as well as the relative presence of TFs and nTFs. Whereas nodes showing explosion of TF numbers belong to multicellular clades, those for nTFs lie among the fungi and the protists.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 5","pages":"Article 168959"},"PeriodicalIF":4.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035712","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

The Critical Role of the Variable Domain in Driving Proteotoxicity and Aggregation in Full-length Light Chains

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-20 DOI: 10.1016/j.jmb.2025.168958

Sarita Puri , Angela Gadda , Ivan Polsinelli , Maria Monica Barzago , Angelo Toto , Manoj Kumar Sriramoju , Cristina Visentin , Luca Broggini , Diane Marie Valérie Bonnet , Rosaria Russo , Antonio Chaves-Sanjuan , Giampaolo Merlini , Mario Nuvolone , Giovanni Palladini , Stefano Gianni , Shang-Te Danny Hsu , Luisa Diomede , Stefano Ricagno

{"title":"The Critical Role of the Variable Domain in Driving Proteotoxicity and Aggregation in Full-length Light Chains","authors":"Sarita Puri , Angela Gadda , Ivan Polsinelli , Maria Monica Barzago , Angelo Toto , Manoj Kumar Sriramoju , Cristina Visentin , Luca Broggini , Diane Marie Valérie Bonnet , Rosaria Russo , Antonio Chaves-Sanjuan , Giampaolo Merlini , Mario Nuvolone , Giovanni Palladini , Stefano Gianni , Shang-Te Danny Hsu , Luisa Diomede , Stefano Ricagno","doi":"10.1016/j.jmb.2025.168958","DOIUrl":"10.1016/j.jmb.2025.168958","url":null,"abstract":"<div><div>Light chain (AL) amyloidosis is the most common systemic amyloid disease characterized by abnormal accumulation of amyloid fibrils derived from immunoglobulin light chains (LCs). Both full-length (FL) LCs and their isolated variable (VL) and constant (CL) domains contribute to amyloid deposits in multiple organs, with the VL domain predominantly forming the fibril core. However, the role and interplay of these domains in amyloid aggregation and toxicity are poorly understood. Characterizing the amyloidogenic λ6-LC AL55, this study explores the properties of both FL and isolated domains and compares them with the available patient-derived data. FL AL55 biophysical features result from the interplay between its VL and CL domains where the limited VL-CL interface might play a major role. Slow refolding kinetic of FL confirms the unfolded VL domain as a kinetic trap possibly shifting the process towards misfolding. The X-ray structure of FL AL55 shows that VL domains may detach from the native dimeric assembly and establish non-native interdimeric interfaces. Additionally, isolated VL domains display significantly lower soluble toxicity compared to FL and do not form fibrils similar to those found <em>ex vivo</em>. Thus the data obtained in this work allowed us to draw a molecular sketch of the aggregation pathway for amyloidogenic LCs.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 5","pages":"Article 168958"},"PeriodicalIF":4.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021542","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