首页 > 最新文献

Journal of Molecular Biology最新文献

英文 中文
Corrigendum to “The Role of ATG9 Vesicles in Autophagosome Biogenesis” [J. Mol. Biol. 436(15) (2024) 168489] ATG9 小泡在自噬体生物生成中的作用》[J. Mol. Biol. 436(15) (2024) 168489]的更正。
IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1016/j.jmb.2024.168849
Elisabeth Holzer , Sascha Martens , Susanna Tulli
{"title":"Corrigendum to “The Role of ATG9 Vesicles in Autophagosome Biogenesis” [J. Mol. Biol. 436(15) (2024) 168489]","authors":"Elisabeth Holzer , Sascha Martens , Susanna Tulli","doi":"10.1016/j.jmb.2024.168849","DOIUrl":"10.1016/j.jmb.2024.168849","url":null,"abstract":"","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168849"},"PeriodicalIF":4.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611395","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
Structural Studies on Mycobacterial NudC Reveal a Class of Zinc Independent NADH Pyrophosphatase 对分枝杆菌 NudC 的结构研究揭示了一类独立于锌的 NADH 焦磷酸酶。
IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-08 DOI: 10.1016/j.jmb.2024.168864
Lingyu Meng , Zhaojian Sun , Yulong Zhang , Yan Dong , Xiaoan Du , Yujian Wu , Yuan Yuan , Yirong Sun , Yong Xu , Huaiwei Ding , Jinsong Liu , Jinxin Xu
Non-tuberculous mycobacteria (NTM) have emerged as an increasing threat to public health, due to the extreme antibiotic resistance. NADH pyrophosphatase (NudC) was proposed involving in mycobacterial resistance to the first line anti-tubercular drug isoniazid (INH) or its analog ethionamide (ETH), by hydrolyzing their NAD modified active forms (NAD-INH and NAD-ETH). In this study, we performed enzymatic and structural studies on NudC from M. abscessus (NudCMab), which is highly resistant to isoniazid and emerging as the most worrisome NTM. We determined the crystal structures of NudCMab in apo form, substrate NAD-bound form and product AMP-bound form. We observed the mode for the Nudix motif of NudCMab capturing the pyrophosphate group of NAD mediated by three divalent cation ions, which provides details for understanding the mechanism on NudC hydrolyzing NAD(H) or NAD-capped substrate. Interestingly, our structures revealed a novel subclass NudC from mycobacteria characterized by a unique arginine residue on the conserved QPWPFPxS motif, as well as a unique tower domain that replaces a well-defined zinc-binding motif in E.coli NudC and catalytic domain of mammalian Nudt12. Thus, our structural studies on NudCMab not only present a class of zinc independent NADH pyrophosphatase in mycobacteria, but also may facilitate the design of NudC inhibitors for the treatment of mycobacteria infections in combination with INH or ETH.
非结核分枝杆菌(NTM)对抗生素具有极强的耐药性,对公共卫生的威胁日益严重。有人提出,NADH焦磷酸酶(NudC)通过水解NAD修饰的活性形式(NAD-INH和NAD-ETH),参与分枝杆菌对一线抗结核药物异烟肼(INH)或其类似物乙硫酰胺(ETH)的耐药性。在本研究中,我们对来自脓肿霉菌的 NudC(NudCMab)进行了酶学和结构研究,脓肿霉菌对异烟肼高度耐药,正在成为最令人担忧的非典型肺炎霉菌。我们测定了 NudCMab 的蛋白酶、底物 NAD 结合型和产物 AMP 结合型晶体结构。我们观察到 NudCMab 的 Nudix 基序在三个二价阳离子的介导下捕获 NAD 的焦磷酸基团的模式,这为了解 NudC 水解 NAD(H) 或 NAD 封闭底物的机制提供了细节。有趣的是,我们的结构发现了一种来自分枝杆菌的新型亚类 NudC,其特点是在保守的 QPWPFPxS 基序上有一个独特的精氨酸残基,还有一个独特的塔状结构域,取代了大肠杆菌 NudC 中定义明确的锌结合基序和哺乳动物 Nudt12 的催化结构域。因此,我们对 NudCMab 的结构研究不仅展示了分枝杆菌中一类锌独立的 NADH 焦磷酸酶,还有助于设计 NudC 抑制剂,与 INH 或 ETH 联用治疗分枝杆菌感染。
{"title":"Structural Studies on Mycobacterial NudC Reveal a Class of Zinc Independent NADH Pyrophosphatase","authors":"Lingyu Meng ,&nbsp;Zhaojian Sun ,&nbsp;Yulong Zhang ,&nbsp;Yan Dong ,&nbsp;Xiaoan Du ,&nbsp;Yujian Wu ,&nbsp;Yuan Yuan ,&nbsp;Yirong Sun ,&nbsp;Yong Xu ,&nbsp;Huaiwei Ding ,&nbsp;Jinsong Liu ,&nbsp;Jinxin Xu","doi":"10.1016/j.jmb.2024.168864","DOIUrl":"10.1016/j.jmb.2024.168864","url":null,"abstract":"<div><div>Non-tuberculous mycobacteria (NTM) have emerged as an increasing threat to public health, due to the extreme antibiotic resistance. NADH pyrophosphatase (NudC) was proposed involving in mycobacterial resistance to the first line anti-tubercular drug isoniazid (INH) or its analog ethionamide (ETH), by hydrolyzing their NAD modified active forms (NAD-INH and NAD-ETH). In this study, we performed enzymatic and structural studies on NudC from <em>M. abscessus</em> (NudC<em><sub>Mab</sub></em>), which is highly resistant to isoniazid and emerging as the most worrisome NTM. We determined the crystal structures of NudC<em><sub>Mab</sub></em> in apo form, substrate NAD-bound form and product AMP-bound form. We observed the mode for the Nudix motif of NudC<em><sub>Mab</sub></em> capturing the pyrophosphate group of NAD mediated by three divalent cation ions, which provides details for understanding the mechanism on NudC hydrolyzing NAD(H) or NAD-capped substrate. Interestingly, our structures revealed a novel subclass NudC from mycobacteria characterized by a unique arginine residue on the conserved QPWPFPxS motif, as well as a unique tower domain that replaces a well-defined zinc-binding motif in <em>E.coli</em> NudC and catalytic domain of mammalian Nudt12. Thus, our structural studies on NudC<em><sub>Mab</sub></em> not only present a class of zinc independent NADH pyrophosphatase in mycobacteria, but also may facilitate the design of NudC inhibitors for the treatment of mycobacteria infections in combination with INH or ETH.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168864"},"PeriodicalIF":4.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611386","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
Stack-AVP: A Stacked Ensemble Predictor Based on Multi-view Information for Fast and Accurate Discovery of Antiviral Peptides. Stack-AVP:基于多视角信息的堆叠集合预测器,用于快速准确地发现抗病毒肽。
IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.jmb.2024.168853
Phasit Charoenkwan, Pramote Chumnanpuen, Nalini Schaduangrat, Watshara Shoombuatong

AVPs, or antiviral peptides, are short chains of amino acids capable of inhibiting viral replication, preventing viral entry, or disrupting viral membranes. They represent a promising area of research for developing new antiviral therapies due to their potential to target a broad spectrum of viruses, incorporating those resistant to traditional antiviral drugs. However, traditional experimental methods for identifying AVPs are often costly and labour-intensive. Thus far, multiple computational methods have been introduced for the in silico identification of AVPs, but these methods still have certain shortcomings. In this study, we propose a novel stacked ensemble learning framework, termed Stack-AVP, for fast and accurate AVP identification. In Stack-AVP, we investigated heterogeneous prediction models, which were trained with 12 commonly used machine learning algorithms coupled with a wide range of multiple feature encoding schemes. Subsequently, these prediction models were adopted to generate multi-view features providing class information and probability information. Finally, we applied our feature selection method to determine the best feature subset for the construction of the final stacked model. Comparative assessments on the independent test dataset revealed that Stack-AVP surpassed the performance of current state-of-the-art methods, with an accuracy of 0.930, MCC of 0.860, and AUC of 0.975. Furthermore, it was found that our multi-view features exhibited a crucial mechanism to improve the prediction performance of AVPs. To facilitate experimental scientists in performing high-throughput identification of AVPs, the prediction sever Stack-AVP is publicly accessible at https://pmlabqsar.pythonanywhere.com/Stack-AVP.

AVPs 或抗病毒肽是能够抑制病毒复制、阻止病毒进入或破坏病毒膜的氨基酸短链。由于抗病毒肽具有靶向多种病毒(包括对传统抗病毒药物产生抗药性的病毒)的潜力,因此是开发新型抗病毒疗法的一个前景广阔的研究领域。然而,用于鉴定 AVPs 的传统实验方法往往成本高昂且劳动密集。迄今为止,已有多种计算方法被引入到反转录病毒蛋白的硅学鉴定中,但这些方法仍存在一定的缺陷。在本研究中,我们提出了一种新型的堆叠集合学习框架,称为 Stack-AVP,用于快速准确地识别 AVP。在 Stack-AVP 中,我们研究了异构预测模型,这些模型由 12 种常用的机器学习算法和多种特征编码方案组成。随后,这些预测模型被用于生成提供类别信息和概率信息的多视角特征。最后,我们采用特征选择方法来确定构建最终叠加模型的最佳特征子集。在独立测试数据集上进行的比较评估显示,Stack-AVP 超越了当前最先进方法的性能,准确率为 0.930,MCC 为 0.860,AUC 为 0.975。此外,研究还发现,我们的多视角特征显示出了提高 AVP 预测性能的关键机制。为了方便实验科学家对 AVPs 进行高通量鉴定,Stack-AVP 的预测结果可在 https://pmlabqsar.pythonanywhere.com/Stack-AVP 网站上公开访问。
{"title":"Stack-AVP: A Stacked Ensemble Predictor Based on Multi-view Information for Fast and Accurate Discovery of Antiviral Peptides.","authors":"Phasit Charoenkwan, Pramote Chumnanpuen, Nalini Schaduangrat, Watshara Shoombuatong","doi":"10.1016/j.jmb.2024.168853","DOIUrl":"10.1016/j.jmb.2024.168853","url":null,"abstract":"<p><p>AVPs, or antiviral peptides, are short chains of amino acids capable of inhibiting viral replication, preventing viral entry, or disrupting viral membranes. They represent a promising area of research for developing new antiviral therapies due to their potential to target a broad spectrum of viruses, incorporating those resistant to traditional antiviral drugs. However, traditional experimental methods for identifying AVPs are often costly and labour-intensive. Thus far, multiple computational methods have been introduced for the in silico identification of AVPs, but these methods still have certain shortcomings. In this study, we propose a novel stacked ensemble learning framework, termed Stack-AVP, for fast and accurate AVP identification. In Stack-AVP, we investigated heterogeneous prediction models, which were trained with 12 commonly used machine learning algorithms coupled with a wide range of multiple feature encoding schemes. Subsequently, these prediction models were adopted to generate multi-view features providing class information and probability information. Finally, we applied our feature selection method to determine the best feature subset for the construction of the final stacked model. Comparative assessments on the independent test dataset revealed that Stack-AVP surpassed the performance of current state-of-the-art methods, with an accuracy of 0.930, MCC of 0.860, and AUC of 0.975. Furthermore, it was found that our multi-view features exhibited a crucial mechanism to improve the prediction performance of AVPs. To facilitate experimental scientists in performing high-throughput identification of AVPs, the prediction sever Stack-AVP is publicly accessible at https://pmlabqsar.pythonanywhere.com/Stack-AVP.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168853"},"PeriodicalIF":4.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602668","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
Validation of the APOBEC3A-Mediated RNA Single Base Substitution Signature and Proposal of Novel APOBEC1, APOBEC3B, and APOBEC3G RNA Signatures 验证 APOBEC3A 介导的 RNA 单碱基替换特征并提出新的 APOBEC1、APOBEC3B 和 APOBEC3G RNA 特征。
IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.jmb.2024.168854
Benjamin Fixman , Marcos Díaz-Gay , Connor Qiu , Tamara Margaryan , Brian Lee , Xiaojiang S. Chen
Mutational signature analysis gained significant attention for providing critical insights into the underlying mutational processes for various DNA single base substitution (SBS) signatures and their associations with different cancer types. Recently, RNA single base substitution (RNA-SBS) signatures were defined and described by decomposing RNA variants found in non-small cell lung cancer. Through statistical association, they attributed Apolipoprotein B mRNA Editing Enzyme, Catalytic Polypeptide 3A (APOBEC3A) mutagenesis to the RNA-SBS2 signature. Here, we provide the first validation of an RNA-SBS mutational signature by decomposing novel exogenous and endogenous APOBEC3A RNA editing signatures into COSMICv3.4 RNA-SBS reference signatures. Additionally, we have identified novel RNA-SBS signatures for APOBEC1, APOBEC3B, and APOBEC3G.
突变特征分析为深入了解各种 DNA 单碱基置换(SBS)特征的潜在突变过程及其与不同癌症类型的关联提供了重要依据,因而备受关注。最近,通过分解在非小细胞肺癌中发现的 RNA 变异,定义并描述了 RNA 单碱基置换(RNA-SBS)特征。通过统计关联,他们将载脂蛋白 B mRNA 编辑酶催化多肽 3A(APOBEC3A)突变归因于 RNA-SBS2 特征。在此,我们通过将新型外源性和内源性 APOBEC3A RNA 编辑特征分解为 COSMICv3.4 RNA-SBS 参考特征,首次验证了 RNA-SBS 突变特征。此外,我们还发现了 APOBEC1、APOBEC3B 和 APOBEC3G 的新型 RNA-SBS 特征。
{"title":"Validation of the APOBEC3A-Mediated RNA Single Base Substitution Signature and Proposal of Novel APOBEC1, APOBEC3B, and APOBEC3G RNA Signatures","authors":"Benjamin Fixman ,&nbsp;Marcos Díaz-Gay ,&nbsp;Connor Qiu ,&nbsp;Tamara Margaryan ,&nbsp;Brian Lee ,&nbsp;Xiaojiang S. Chen","doi":"10.1016/j.jmb.2024.168854","DOIUrl":"10.1016/j.jmb.2024.168854","url":null,"abstract":"<div><div>Mutational signature analysis gained significant attention for providing critical insights into the underlying mutational processes for various DNA single base substitution (SBS) signatures and their associations with different cancer types. Recently, RNA single base substitution (RNA-SBS) signatures were defined and described by decomposing RNA variants found in non-small cell lung cancer. Through statistical association, they attributed Apolipoprotein B mRNA Editing Enzyme, Catalytic Polypeptide 3A (APOBEC3A) mutagenesis to the RNA-SBS2 signature. Here, we provide the first validation of an RNA-SBS mutational signature by decomposing novel exogenous and endogenous APOBEC3A RNA editing signatures into COSMICv3.4 RNA-SBS reference signatures. Additionally, we have identified novel RNA-SBS signatures for APOBEC1, APOBEC3B, and APOBEC3G.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 24","pages":"Article 168854"},"PeriodicalIF":4.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602688","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
Revealing Missing Protein–Ligand Interactions Using AlphaFold Predictions 利用 AlphaFold 预测揭示缺失的蛋白质配体相互作用。
IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.jmb.2024.168852
Nahuel Escobedo , Tadeo Saldaño , Juan Mac Donagh , Luciana Rodriguez Sawicki , Nicolas Palopoli , Sebastian Fernandez Alberti , Maria Silvina Fornasari , Gustavo Parisi
Protein–ligand interactions represent an essential step to understand the bases of molecular recognition, an intense field of research in many scientific areas. Structural biology has played a central role in unveiling protein–ligand interactions, but current techniques are still not able to reliably describe the interactions of ligands with highly flexible regions. In this work, we explored the capacity of AlphaFold2 (AF2) to estimate the presence of interactions between ligands and residues belonging to disordered regions. As these interactions are missing in the crystallographic-derived structures, we called them “ghost interactions”. Using a set of protein structures experimentally obtained after AF2 was trained, we found that the obtained models are good predictors of regions associated with order–disorder transitions. Additionally, we found that AF2 predicts residues making ghost interactions with ligands, which are mostly buried and show differential evolutionary conservation with the rest of the residues located in the flexible region. Our findings could fuel current areas of research that consider, given their biological relevance and their involvement in diseases, intrinsically disordered proteins as potentially valuable targets for drug development.
蛋白质与配体的相互作用是了解分子识别基础的重要一步,也是许多科学领域的热门研究领域。结构生物学在揭示蛋白质-配体相互作用方面发挥了核心作用,但目前的技术仍无法可靠地描述配体与高柔性区域的相互作用。在这项工作中,我们探索了 AlphaFold2(AF2)估计配体与属于无序区域的残基之间是否存在相互作用的能力。由于这些相互作用在晶体学结构中缺失,我们称之为 "幽灵相互作用"。通过使用一组经过 AF2 训练后通过实验获得的蛋白质结构,我们发现所获得的模型可以很好地预测与有序-无序转换相关的区域。此外,我们还发现 AF2 可以预测与配体发生鬼影作用的残基,这些残基大多被埋藏,并与位于柔性区域的其他残基显示出不同的进化守恒性。鉴于内在无序蛋白质的生物学相关性及其与疾病的关系,我们的研究结果可以推动当前的研究领域,使其成为有价值的潜在药物开发目标。
{"title":"Revealing Missing Protein–Ligand Interactions Using AlphaFold Predictions","authors":"Nahuel Escobedo ,&nbsp;Tadeo Saldaño ,&nbsp;Juan Mac Donagh ,&nbsp;Luciana Rodriguez Sawicki ,&nbsp;Nicolas Palopoli ,&nbsp;Sebastian Fernandez Alberti ,&nbsp;Maria Silvina Fornasari ,&nbsp;Gustavo Parisi","doi":"10.1016/j.jmb.2024.168852","DOIUrl":"10.1016/j.jmb.2024.168852","url":null,"abstract":"<div><div>Protein–ligand interactions represent an essential step to understand the bases of molecular recognition, an intense field of research in many scientific areas. Structural biology has played a central role in unveiling protein–ligand interactions, but current techniques are still not able to reliably describe the interactions of ligands with highly flexible regions. In this work, we explored the capacity of AlphaFold2 (AF2) to estimate the presence of interactions between ligands and residues belonging to disordered regions. As these interactions are missing in the crystallographic-derived structures, we called them “ghost interactions”. Using a set of protein structures experimentally obtained after AF2 was trained, we found that the obtained models are good predictors of regions associated with order–disorder transitions. Additionally, we found that AF2 predicts residues making ghost interactions with ligands, which are mostly buried and show differential evolutionary conservation with the rest of the residues located in the flexible region. Our findings could fuel current areas of research that consider, given their biological relevance and their involvement in diseases, intrinsically disordered proteins as potentially valuable targets for drug development.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168852"},"PeriodicalIF":4.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602664","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 Discovery for Diseases with High Unmet Need Through Perturbation of Biomolecular Condensates 通过扰动生物分子凝集物,发现治疗需求量大的疾病的药物。
IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.jmb.2024.168855
Bahareh Eftekharzadeh, Aislinn Mayfield, Michael G. Kauffman, John F. Reilly
Biomolecular condensates (BMCs), play significant roles in organizing cellular functions in the absence of membranes through phase separation events involving RNA, proteins, and RNA-protein complexes. These membrane-less organelles form dynamic multivalent weak interactions, often involving intrinsically disordered proteins or regions (IDPs/IDRs). However, the nature of these crucial interactions, how most of these organelles are organized and are functional, remains unknown. Aberrant condensates have been implicated in neurodegenerative diseases and various cancers, presenting novel therapeutic opportunities for small molecule condensate modulators. Recent advancements in optogenetic technologies, particularly Corelet, enable precise manipulation of BMC dynamics within living cells, facilitating high-throughput screening for small molecules that target these complex structures. By elucidating the molecular mechanisms governing BMC formation and function, this innovative approach holds promise to unlock therapeutic strategies against previously “undruggable” protein targets, paving the way for effective interventions in disease.
生物分子凝聚体(BMC)通过涉及 RNA、蛋白质和 RNA 蛋白复合物的相分离事件,在无膜情况下组织细胞功能方面发挥着重要作用。这些无膜细胞器形成动态的多价弱相互作用,通常涉及内在无序蛋白或区域(IDPs/IDRs)。然而,这些关键性相互作用的性质,以及大多数细胞器是如何组织起来并发挥功能的,仍然不得而知。异常凝聚物与神经退行性疾病和各种癌症有关,为小分子凝聚物调节剂提供了新的治疗机会。光遗传学技术(尤其是 Corelet)的最新进展使人们能够精确操纵活细胞内的 BMC 动态,从而促进了针对这些复杂结构的小分子药物的高通量筛选。通过阐明支配 BMC 形成和功能的分子机制,这种创新方法有望针对以前 "无法治疗 "的蛋白质靶点开启治疗策略,为有效干预疾病铺平道路。
{"title":"Drug Discovery for Diseases with High Unmet Need Through Perturbation of Biomolecular Condensates","authors":"Bahareh Eftekharzadeh,&nbsp;Aislinn Mayfield,&nbsp;Michael G. Kauffman,&nbsp;John F. Reilly","doi":"10.1016/j.jmb.2024.168855","DOIUrl":"10.1016/j.jmb.2024.168855","url":null,"abstract":"<div><div>Biomolecular condensates (BMCs), play significant roles in organizing cellular functions in the absence of membranes through phase separation events involving RNA, proteins, and RNA-protein complexes. These membrane-less organelles form dynamic multivalent weak interactions, often involving intrinsically disordered proteins or regions (IDPs/IDRs). However, the nature of these crucial interactions, how most of these organelles are organized and are functional, remains unknown. Aberrant condensates have been implicated in neurodegenerative diseases and various cancers, presenting novel therapeutic opportunities for small molecule condensate modulators. Recent advancements in optogenetic technologies, particularly Corelet, enable precise manipulation of BMC dynamics within living cells, facilitating high-throughput screening for small molecules that target these complex structures. By elucidating the molecular mechanisms governing BMC formation and function, this innovative approach holds promise to unlock therapeutic strategies against previously “undruggable” protein targets, paving the way for effective interventions in disease.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168855"},"PeriodicalIF":4.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602659","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
MST-m6A: A Novel Multi-Scale Transformer-based Framework for Accurate Prediction of m6A Modification Sites Across Diverse Cellular Contexts. MST-m6A:基于多尺度变换器的新型框架,用于准确预测不同细胞环境中的 m6A 修饰位点。
IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.jmb.2024.168856
Qiaosen Su, Le Thi Phan, Nhat Truong Pham, Leyi Wei, Balachandran Manavalan

N6-methyladenosine (m6A) modification, a prevalent epigenetic mark in eukaryotic cells, is crucial in regulating gene expression and RNA metabolism. Accurately identifying m6A modification sites is essential for understanding their functions within biological processes and the intricate mechanisms that regulate them. Recent advances in high-throughput sequencing technologies have enabled the generation of extensive datasets characterizing m6A modification sites at single-nucleotide resolution, leading to the development of computational methods for identifying m6A RNA modification sites. However, most current methods focus on specific cell lines, limiting their generalizability and practical application across diverse biological contexts. To address the limitation, we propose MST-m6A, a novel approach for identifying m6A modification sites with higher accuracy across various cell lines and tissues. MST-m6A utilizes a multi-scale transformer-based architecture, employing dual k-mer tokenization to capture rich feature representations and global contextual information from RNA sequences at multiple levels of granularity. These representations are then effectively combined using a channel fusion mechanism and further processed by a convolutional neural network to enhance prediction accuracy. Rigorous validation demonstrates that MST-m6A significantly outperforms conventional machine learning models, deep learning models, and state-of-the-art predictors. We anticipate that the high precision and cross-cell-type adaptability of MST-m6A will provide valuable insights into m6A biology and facilitate advancements in related fields. The proposed approach is available at https://github.com/cbbl-skku-org/MST-m6A/ for prediction and reproducibility purposes.

N6-甲基腺苷(m6A)修饰是真核细胞中一种普遍存在的表观遗传标记,在调控基因表达和 RNA 代谢方面至关重要。准确鉴定 m6A 修饰位点对于了解它们在生物过程中的功能以及调控它们的复杂机制至关重要。高通量测序技术的最新进展使得人们能够生成大量数据集,以单核苷酸分辨率描述 m6A 修饰位点的特征,从而开发出用于鉴定 m6A RNA 修饰位点的计算方法。然而,目前的大多数方法都集中在特定的细胞系上,限制了它们在不同生物环境中的通用性和实际应用。为了解决这一限制,我们提出了 MST-m6A,这是一种在不同细胞系和组织中以更高准确度鉴定 m6A 修饰位点的新方法。MST-m6A 利用基于多尺度变换器的架构,采用双 k-mer 标记化技术,从多级粒度的 RNA 序列中捕捉丰富的特征表征和全局上下文信息。然后利用通道融合机制将这些表征有效地结合起来,并通过卷积神经网络进一步处理,以提高预测准确性。严格的验证表明,MST-m6A 的性能明显优于传统的机器学习模型、深度学习模型和最先进的预测器。我们预计,MST-m6A 的高精度和跨细胞类型适应性将为 m6A 生物学提供有价值的见解,并促进相关领域的进步。所提出的方法可在 https://github.com/cbbl-skku-org/MST-m6A/ 上进行预测和重现。
{"title":"MST-m6A: A Novel Multi-Scale Transformer-based Framework for Accurate Prediction of m6A Modification Sites Across Diverse Cellular Contexts.","authors":"Qiaosen Su, Le Thi Phan, Nhat Truong Pham, Leyi Wei, Balachandran Manavalan","doi":"10.1016/j.jmb.2024.168856","DOIUrl":"10.1016/j.jmb.2024.168856","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) modification, a prevalent epigenetic mark in eukaryotic cells, is crucial in regulating gene expression and RNA metabolism. Accurately identifying m6A modification sites is essential for understanding their functions within biological processes and the intricate mechanisms that regulate them. Recent advances in high-throughput sequencing technologies have enabled the generation of extensive datasets characterizing m6A modification sites at single-nucleotide resolution, leading to the development of computational methods for identifying m6A RNA modification sites. However, most current methods focus on specific cell lines, limiting their generalizability and practical application across diverse biological contexts. To address the limitation, we propose MST-m6A, a novel approach for identifying m6A modification sites with higher accuracy across various cell lines and tissues. MST-m6A utilizes a multi-scale transformer-based architecture, employing dual k-mer tokenization to capture rich feature representations and global contextual information from RNA sequences at multiple levels of granularity. These representations are then effectively combined using a channel fusion mechanism and further processed by a convolutional neural network to enhance prediction accuracy. Rigorous validation demonstrates that MST-m6A significantly outperforms conventional machine learning models, deep learning models, and state-of-the-art predictors. We anticipate that the high precision and cross-cell-type adaptability of MST-m6A will provide valuable insights into m6A biology and facilitate advancements in related fields. The proposed approach is available at https://github.com/cbbl-skku-org/MST-m6A/ for prediction and reproducibility purposes.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168856"},"PeriodicalIF":4.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602661","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
Determinants in the HTLV-1 Capsid Major Homology Region that are Critical for Virus Particle Assembly 对病毒粒子组装至关重要的 HTLV-1 荚膜主要同源区的决定因素。
IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-05 DOI: 10.1016/j.jmb.2024.168851
Huixin Yang , William G. Arndt , Wei Zhang , Louis M. Mansky
The Gag protein of retroviruses is the primary driver of virus particle assembly. Particle morphologies among retroviral genera are distinct, with intriguing differences observed relative to human immunodeficiency virus type 1 (HIV-1), particularly that of human T-cell leukemia virus type 1 (HTLV-1). In contrast to HIV-1 and other retroviruses where the capsid (CA) carboxy-terminal domain (CTD) possesses the key amino acid determinants involved in driving Gag-Gag interactions, we have previously demonstrated that the amino-terminal domain (NTD) encodes the key residues crucial for Gag multimerization and immature particle production. Here in this study, we sought to thoroughly interrogate the conserved HTLV-1 major homology region (MHR) of the CACTD to determine whether this region harbors residues important for particle assembly. In particular, site-directed mutagenesis of the HTLV-1 MHR was conducted, and mutants were analyzed for their ability to impact Gag subcellular distribution, particle production and morphology, as well as the CA-CA assembly kinetics. Several key residues (i.e., Q138, E142, Y144, F147 and R150), were found to significantly impact Gag multimerization and particle assembly. Taken together, these observations imply that while the HTLV-1 CANTD acts as the major region involved in CA-CA interactions, residues in the MHR can impact Gag multimerization, particle assembly and morphology, and likely play an important role in the conformation the CACTD that is required for CA-CA interactions.
逆转录病毒的 Gag 蛋白是病毒粒子组装的主要驱动力。逆转录病毒属之间的粒子形态各不相同,与 HIV-1 相比,尤其是人类 T 细胞白血病病毒 1 型(HTLV-1)的粒子形态存在着令人费解的差异。HIV-1 和其他逆转录病毒的噬菌体(CA)羧基末端结构域(CTD)具有参与驱动 Gag-Gag 相互作用的关键氨基酸决定因子,与此不同的是,我们以前已经证明氨基末端结构域(NTD)编码了对 Gag 多聚化和未成熟颗粒生成至关重要的关键残基。在本研究中,我们试图彻底检查 CACTD 的保守 HTLV-1 主要同源区 (MHR),以确定该区域是否含有对粒子组装至关重要的残基。特别是,我们对 HTLV-1 MHR 进行了定点突变,并分析了突变体对 Gag 亚细胞分布、颗粒生成和形态以及 CA-CA 组装动力学的影响。研究发现,几个关键残基(即 Q138、E142、Y144、F147 和 R150)对 Gag 的多聚化和颗粒组装有显著影响。综上所述,这些观察结果表明,虽然 HTLV-1 CANTD 是参与 CA-CA 相互作用的主要区域,但 MHR 中的残基也会影响 Gag 的多聚化、粒子组装和形态,并可能在 CA-CA 相互作用所需的 CACTD 构象中发挥重要作用。
{"title":"Determinants in the HTLV-1 Capsid Major Homology Region that are Critical for Virus Particle Assembly","authors":"Huixin Yang ,&nbsp;William G. Arndt ,&nbsp;Wei Zhang ,&nbsp;Louis M. Mansky","doi":"10.1016/j.jmb.2024.168851","DOIUrl":"10.1016/j.jmb.2024.168851","url":null,"abstract":"<div><div>The Gag protein of retroviruses is the primary driver of virus particle assembly. Particle morphologies among retroviral genera are distinct, with intriguing differences observed relative to human immunodeficiency virus type 1 (HIV-1), particularly that of human T-cell leukemia virus type 1 (HTLV-1). In contrast to HIV-1 and other retroviruses where the capsid (CA) carboxy-terminal domain (CTD) possesses the key amino acid determinants involved in driving Gag-Gag interactions, we have previously demonstrated that the amino-terminal domain (NTD) encodes the key residues crucial for Gag multimerization and immature particle production. Here in this study, we sought to thoroughly interrogate the conserved HTLV-1 major homology region (MHR) of the CA<sub>CTD</sub> to determine whether this region harbors residues important for particle assembly. In particular, site-directed mutagenesis of the HTLV-1 MHR was conducted, and mutants were analyzed for their ability to impact Gag subcellular distribution, particle production and morphology, as well as the CA-CA assembly kinetics. Several key residues (<em>i.e.</em>, Q138, E142, Y144, F147 and R150), were found to significantly impact Gag multimerization and particle assembly. Taken together, these observations imply that while the HTLV-1 CA<sub>NTD</sub> acts as the major region involved in CA-CA interactions, residues in the MHR can impact Gag multimerization, particle assembly and morphology, and likely play an important role in the conformation the CA<sub>CTD</sub> that is required for CA-CA interactions.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 24","pages":"Article 168851"},"PeriodicalIF":4.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589675","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
Pim1 is Critical in T-cell-independent B-cell Response and MAPK Activation in B Cells Pim1 在 B 细胞的独立于 T 细胞的 B 细胞反应和 MAPK 激活中至关重要。
IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-04 DOI: 10.1016/j.jmb.2024.168824
Dongya Cui , Yongguang Zhang , Baijiao Zheng , Liling Chen , Jianhui Wei , Danfeng Lin , Miaohui Huang , Hekang Du , Qi Chen
The Pim family consists of three members that encode a distinct class of highly conserved serine/threonine kinases. In this study, we generated and examined mice with hematopoiesis-specific deletion of Pim1 and bone marrow (BM) chimeric mice with B-cell-specific targeted deletion of Pim1. Pim1 was expressed at all stages of B-cell development and hematopoietic-specific deletion of Pim1 altered B-cell development in BM, spleen and peritoneal. However, Pim1 deficiency did not affect T-cell development. Studies of BM chimeric mice showed that Pim1 is required in a cell-intrinsic manner to maintain normal B-cell development. Pim1 deficiency led to significant changes in B cell antibody responses. Additionally, Pim1 deficiency resulted in reduced B cell receptor (BCR)-induced cell proliferation and cell cycle progression. Examination of the various BCR-activated signaling pathways in Pim1-deficient B cells reveals defective activation of mitogen-activated protein kinases (MAPKs), which are known to regulate genes involved in cell proliferation and survival. qRT-PCR analysis of BCR-engaged B cells from Pim1-deficient B cells revealed reduced expression of cyclin-dependent kinase (CDK) and cyclin genes, including CDK2, CCNB1 and CCNE1. In conclusion, Pim1 plays a crucial role in B-cell development and B cell activation.
Pim 家族由三个成员组成,它们编码一类不同的高度保守的丝氨酸/苏氨酸激酶。在这项研究中,我们产生并研究了造血特异性缺失 Pim1 的小鼠和骨髓(BM)嵌合体小鼠。Pim1 在 B 细胞发育的各个阶段都有表达,造血特异性缺失 Pim1 会改变 BM、脾脏和腹膜中 B 细胞的发育。然而,Pim1 的缺失并不影响 T 细胞的发育。对BM嵌合小鼠的研究表明,Pim1需要以细胞内在方式维持正常的B细胞发育。Pim1 缺乏会导致 B 细胞抗体反应发生显著变化。此外,Pim1 缺乏还会导致 B 细胞受体(BCR)诱导的细胞增殖和细胞周期进展减少。对 Pim1 缺乏的 B 细胞中 BCR 激活的各种信号通路进行的研究发现,丝裂原活化蛋白激酶(MAPKs)的激活存在缺陷,而众所周知,MAPKs 可调节参与细胞增殖和存活的基因;对 Pim1 缺乏的 B 细胞中 BCR 激活的 B 细胞进行的 qRT-PCR 分析显示,细胞周期蛋白依赖性激酶(CDK)和细胞周期蛋白基因(包括 CDK2、CCNB1 和 CCNE1)的表达减少。总之,Pim1 在 B 细胞发育和 B 细胞活化中起着至关重要的作用。
{"title":"Pim1 is Critical in T-cell-independent B-cell Response and MAPK Activation in B Cells","authors":"Dongya Cui ,&nbsp;Yongguang Zhang ,&nbsp;Baijiao Zheng ,&nbsp;Liling Chen ,&nbsp;Jianhui Wei ,&nbsp;Danfeng Lin ,&nbsp;Miaohui Huang ,&nbsp;Hekang Du ,&nbsp;Qi Chen","doi":"10.1016/j.jmb.2024.168824","DOIUrl":"10.1016/j.jmb.2024.168824","url":null,"abstract":"<div><div>The Pim family consists of three members that encode a distinct class of highly conserved serine/threonine kinases. In this study, we generated and examined mice with hematopoiesis-specific deletion of Pim1 and bone marrow (BM) chimeric mice with B-cell-specific targeted deletion of Pim1. Pim1 was expressed at all stages of B-cell development and hematopoietic-specific deletion of Pim1 altered B-cell development in BM, spleen and peritoneal. However, Pim1 deficiency did not affect T-cell development. Studies of BM chimeric mice showed that Pim1 is required in a cell-intrinsic manner to maintain normal B-cell development. Pim1 deficiency led to significant changes in B cell antibody responses. Additionally, Pim1 deficiency resulted in reduced B cell receptor (BCR)-induced cell proliferation and cell cycle progression. Examination of the various BCR-activated signaling pathways in Pim1-deficient B cells reveals defective activation of mitogen-activated protein kinases (MAPKs), which are known to regulate genes involved in cell proliferation and survival. qRT-PCR analysis of BCR-engaged B cells from Pim1-deficient B cells revealed reduced expression of cyclin-dependent kinase (CDK) and cyclin genes, including CDK2, CCNB1 and CCNE1. In conclusion, Pim1 plays a crucial role in B-cell development and B cell activation.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168824"},"PeriodicalIF":4.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589676","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
A Nanobody Toolbox for Recognizing Distinct Epitopes on Cas9 用于识别 Cas9 上不同表位的纳米抗体工具箱。
IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-30 DOI: 10.1016/j.jmb.2024.168836
Jack Boylan , Rebecca A Shrem , Isabel C. Vallecillo-Viejo , Craig L. Duvall , Brian E. Wadzinski , Benjamin W. Spiller
Cas9s and fusions of Cas9s have emerged as powerful tools for genetic manipulations. Fusions of Cas9 with other DNA editing enzymes have led to variants capable of single base editing and catalytically dead Cas9s have emerged as tools to specifically target desired regions of a genome. Here we describe the generation of a panel of nanobodies directed against three unique epitopes on Streptococcus pyogenes Cas9. The nanobodies were identified from a nanobody library derived from an alpaca that had been immunized with Cas9. The most potent binders recognize Cas9 and RNA bound Cas9 equally well and do not inhibit Cas9 cleavage of target DNA. These nanobodies bind non-overlapping epitopes as determined by ELISA based epitope binning experiments and mass photometry. We present the sequences of these clones and supporting biochemical data so the broader scientific community can access these reagents.
Cas9s 和 Cas9s 融合体已成为基因操作的强大工具。Cas9与其他DNA编辑酶的融合产生了能够进行单碱基编辑的变体,而催化死亡的Cas9则成为了特异性靶向基因组所需区域的工具。在这里,我们描述了针对化脓性链球菌 Cas9 上的三个独特表位生成纳米抗体的过程。这些纳米抗体是从用 Cas9 免疫的羊驼身上提取的纳米抗体库中鉴定出来的。最有效的结合体同样能识别Cas9和RNA结合的Cas9,而且不会抑制Cas9裂解靶DNA。根据基于酶联免疫吸附法的表位分选实验和质量光度测定法确定,这些纳米抗体结合的表位并不重叠。我们介绍了这些克隆的序列和支持性生化数据,以便更广泛的科学界能够获得这些试剂。
{"title":"A Nanobody Toolbox for Recognizing Distinct Epitopes on Cas9","authors":"Jack Boylan ,&nbsp;Rebecca A Shrem ,&nbsp;Isabel C. Vallecillo-Viejo ,&nbsp;Craig L. Duvall ,&nbsp;Brian E. Wadzinski ,&nbsp;Benjamin W. Spiller","doi":"10.1016/j.jmb.2024.168836","DOIUrl":"10.1016/j.jmb.2024.168836","url":null,"abstract":"<div><div>Cas9s and fusions of Cas9s have emerged as powerful tools for genetic manipulations. Fusions of Cas9 with other DNA editing enzymes have led to variants capable of single base editing and catalytically dead Cas9s have emerged as tools to specifically target desired regions of a genome. Here we describe the generation of a panel of nanobodies directed against three unique epitopes on <em>Streptococcus pyogenes</em> Cas9. The nanobodies were identified from a nanobody library derived from an alpaca that had been immunized with Cas9. The most potent binders recognize Cas9 and RNA bound Cas9 equally well and do not inhibit Cas9 cleavage of target DNA. These nanobodies bind non-overlapping epitopes as determined by ELISA based epitope binning experiments and mass photometry. We present the sequences of these clones and supporting biochemical data so the broader scientific community can access these reagents.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168836"},"PeriodicalIF":4.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556804","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
期刊
Journal of Molecular Biology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
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
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1