Journal of Biomolecular NMR最新文献_第10页

FID-Net: A versatile deep neural network architecture for NMR spectral reconstruction and virtual decoupling FID-Net:用于核磁共振光谱重建和虚拟解耦的通用深度神经网络架构

IF 2.7 3区生物学

Journal of Biomolecular NMR Pub Date : 2021-04-19 DOI: 10.1007/s10858-021-00366-w

Gogulan Karunanithy, D. Flemming Hansen

{"title":"FID-Net: A versatile deep neural network architecture for NMR spectral reconstruction and virtual decoupling","authors":"Gogulan Karunanithy, D. Flemming Hansen","doi":"10.1007/s10858-021-00366-w","DOIUrl":"https://doi.org/10.1007/s10858-021-00366-w","url":null,"abstract":"In recent years, the transformative potential of deep neural networks (DNNs) for analysing and interpreting NMR data has clearly been recognised. However, most applications of DNNs in NMR to date either struggle to outperform existing methodologies or are limited in scope to a narrow range of data that closely resemble the data that the network was trained on. These limitations have prevented a widescale uptake of DNNs in NMR. Addressing this, we introduce FID-Net, a deep neural network architecture inspired by WaveNet, for performing analyses on time domain NMR data. We first demonstrate the effectiveness of this architecture in reconstructing non-uniformly sampled (NUS) biomolecular NMR spectra. It is shown that a single network is able to reconstruct a diverse range of 2D NUS spectra that have been obtained with arbitrary sampling schedules, with a range of sweep widths, and a variety of other acquisition parameters. The performance of the trained FID-Net in this case exceeds or matches existing methods currently used for the reconstruction of NUS NMR spectra. Secondly, we present a network based on the FID-Net architecture that can efficiently virtually decouple 13Cα-13Cβ couplings in HNCA protein NMR spectra in a single shot analysis, while at the same time leaving glycine residues unmodulated. The ability for these DNNs to work effectively in a wide range of scenarios, without retraining, paves the way for their widespread usage in analysing NMR data.","PeriodicalId":613,"journal":{"name":"Journal of Biomolecular NMR","volume":"75 4-5","pages":"179 - 191"},"PeriodicalIF":2.7,"publicationDate":"2021-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10858-021-00366-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4739617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 26

A COVID moonshot: assessment of ligand binding to the SARS-CoV-2 main protease by saturation transfer difference NMR spectroscopy COVID登月计划:利用饱和转移差核磁共振光谱评估配体与SARS-CoV-2主要蛋白酶的结合

IF 2.7 3区生物学

Journal of Biomolecular NMR Pub Date : 2021-04-15 DOI: 10.1007/s10858-021-00365-x

Anastassia L. Kantsadi, Emma Cattermole, Minos-Timotheos Matsoukas, Georgios A. Spyroulias, Ioannis Vakonakis

{"title":"A COVID moonshot: assessment of ligand binding to the SARS-CoV-2 main protease by saturation transfer difference NMR spectroscopy","authors":"Anastassia L. Kantsadi, Emma Cattermole, Minos-Timotheos Matsoukas, Georgios A. Spyroulias, Ioannis Vakonakis","doi":"10.1007/s10858-021-00365-x","DOIUrl":"https://doi.org/10.1007/s10858-021-00365-x","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of the coronavirus disease 2019, for which no effective antiviral therapeutics are available. The SARS-CoV-2 main protease (Mpro) is essential for viral replication and constitutes a promising therapeutic target. Many efforts aimed at deriving effective Mpro inhibitors are currently underway, including an international open-science discovery project, codenamed COVID Moonshot. As part of COVID Moonshot, we used saturation transfer difference nuclear magnetic resonance (STD-NMR) spectroscopy to assess the binding of putative Mpro ligands to the viral protease, including molecules identified by crystallographic fragment screening and novel compounds designed as Mpro inhibitors. In this manner, we aimed to complement enzymatic activity assays of Mpro performed by other groups with information on ligand affinity. We have made the Mpro STD-NMR data publicly available. Here, we provide detailed information on the NMR protocols used and challenges faced, thereby placing these data into context. Our goal is to assist the interpretation of Mpro STD-NMR data, thereby accelerating ongoing drug design efforts.","PeriodicalId":613,"journal":{"name":"Journal of Biomolecular NMR","volume":"75 4-5","pages":"167 - 178"},"PeriodicalIF":2.7,"publicationDate":"2021-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10858-021-00365-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4598986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 4

Comparative analysis of 13C chemical shifts of β-sheet amyloid proteins and outer membrane proteins β-片淀粉样蛋白与外膜蛋白13C化学位移的比较分析

IF 2.7 3区生物学

Journal of Biomolecular NMR Pub Date : 2021-04-12 DOI: 10.1007/s10858-021-00364-y

Noah H. Somberg, Martin D. Gelenter, Mei Hong

{"title":"Comparative analysis of 13C chemical shifts of β-sheet amyloid proteins and outer membrane proteins","authors":"Noah H. Somberg, Martin D. Gelenter, Mei Hong","doi":"10.1007/s10858-021-00364-y","DOIUrl":"https://doi.org/10.1007/s10858-021-00364-y","url":null,"abstract":"Cross-β amyloid fibrils and membrane-bound β-barrels are two important classes of β-sheet proteins. To investigate whether there are systematic differences in the backbone and sidechain conformations of these two families of proteins, here we analyze the 13C chemical shifts of 17 amyloid proteins and 7 β-barrel membrane proteins whose high-resolution structures have been determined by NMR. These 24 proteins contain 373 β-sheet residues in amyloid fibrils and 521 β-sheet residues in β-barrel membrane proteins. The 13C chemical shifts are shown in 2D 13C–13C correlation maps, and the amino acid residues are categorized by two criteria: (1) whether they occur in β-strand segments or in loops and turns; (2) whether they are water-exposed or dry, facing other residues or lipids. We also examine the abundance of each amino acid in amyloid proteins and β-barrels and compare the sidechain rotameric populations. The 13C chemical shifts indicate that hydrophobic methyl-rich residues and aromatic residues exhibit larger static sidechain conformational disorder in amyloid fibrils than in β-barrels. In comparison, hydroxyl- and amide-containing polar residues have more ordered sidechains and more ordered backbones in amyloid fibrils than in β-barrels. These trends can be explained by steric zipper interactions between β-sheet planes in cross-β fibrils, and by the interactions of β-barrel residues with lipid and water in the membrane. These conformational trends should be useful for structural analysis of amyloid fibrils and β-barrels based principally on NMR chemical shifts.","PeriodicalId":613,"journal":{"name":"Journal of Biomolecular NMR","volume":"75 4-5","pages":"151 - 166"},"PeriodicalIF":2.7,"publicationDate":"2021-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10858-021-00364-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4481541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 1

NMR refinement and peptide folding using the GROMACS software 使用GROMACS软件进行核磁共振细化和肽折叠

IF 2.7 3区生物学

Journal of Biomolecular NMR Pub Date : 2021-03-28 DOI: 10.1007/s10858-021-00363-z

Anna Sinelnikova, David van der Spoel

引用次数: 8

How wide is the window opened by high-resolution relaxometry on the internal dynamics of proteins in solution? 高分辨率弛豫测量法对溶液中蛋白质内部动力学的影响有多大?

IF 2.7 3区生物学

Journal of Biomolecular NMR Pub Date : 2021-03-23 DOI: 10.1007/s10858-021-00361-1

Albert A. Smith, Nicolas Bolik-Coulon, Matthias Ernst, Beat H. Meier, Fabien Ferrage

{"title":"How wide is the window opened by high-resolution relaxometry on the internal dynamics of proteins in solution?","authors":"Albert A. Smith, Nicolas Bolik-Coulon, Matthias Ernst, Beat H. Meier, Fabien Ferrage","doi":"10.1007/s10858-021-00361-1","DOIUrl":"https://doi.org/10.1007/s10858-021-00361-1","url":null,"abstract":"The dynamics of molecules in solution is usually quantified by the determination of timescale-specific amplitudes of motions. High-resolution nuclear magnetic resonance (NMR) relaxometry experiments—where the sample is transferred to low fields for longitudinal (T1) relaxation, and back to high field for detection with residue-specific resolution—seeks to increase the ability to distinguish the contributions from motion on timescales slower than a few nanoseconds. However, tumbling of a molecule in solution masks some of these motions. Therefore, we investigate to what extent relaxometry improves timescale resolution, using the “detector” analysis of dynamics. Here, we demonstrate improvements in the characterization of internal dynamics of methyl-bearing side chains by carbon-13 relaxometry in the small protein ubiquitin. We show that relaxometry data leads to better information about nanosecond motions as compared to high-field relaxation data only. Our calculations show that gains from relaxometry are greater with increasing correlation time of rotational diffusion.","PeriodicalId":613,"journal":{"name":"Journal of Biomolecular NMR","volume":"75 2-3","pages":"119 - 131"},"PeriodicalIF":2.7,"publicationDate":"2021-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10858-021-00361-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4904961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 8

Combined multi‐band decoupling in biomolecular NMR spectroscopy 生物分子核磁共振波谱中的联合多波段解耦

IF 2.7 3区生物学

Journal of Biomolecular NMR Pub Date : 2021-03-22 DOI: 10.1007/s10858-021-00360-2

Clemens Anklin, R. Andrew Byrd

引用次数: 3

Removal of 2H-decoupling sidebands in 13CHD2 13C-CEST profiles 13CHD2 - 13C-CEST剖面中h -去耦边带的去除

IF 2.7 3区生物学

Journal of Biomolecular NMR Pub Date : 2021-03-20 DOI: 10.1007/s10858-021-00362-0

Youlin Xia, Tairan Yuwen, Aizhuo Liu, Charalampos G. Kalodimos

{"title":"Removal of 2H-decoupling sidebands in 13CHD2 13C-CEST profiles","authors":"Youlin Xia, Tairan Yuwen, Aizhuo Liu, Charalampos G. Kalodimos","doi":"10.1007/s10858-021-00362-0","DOIUrl":"https://doi.org/10.1007/s10858-021-00362-0","url":null,"abstract":"A unique aspect of NMR is its capacity to provide integrated insight into both the structure and intrinsic dynamics of biomolecules. Chemical exchange phenomena that often serve as probes of dynamic processes in biological macromolecules can be quantitatively investigated with chemical exchange saturation transfer (CEST) experiments. 2H-decoupling sidebands, however, always occur in the profiles of 13CHD2 13C-CEST experiments when using the simple CW (continuous wave) method, which may obscure the detection of minor dips of excited states. Traditionally, these sidebands are manually eliminated from the profiles before data analysis by removing experimental points in the range of 2H-decoupling field strength?±50?Hz away from the major dips of the ground state on either side of the dips. Unfortunately, this may also eliminate potential minor dips if they overlap with the decoupling sidebands. Here, we developed methods that use pseudo-continuous waves with variable RF amplitudes distributed onto ramps for 2H decoupling. The new methods were thoroughly validated on Bruker spectrometers at a range of fields (1H frequencies of 600, 700, and 850?MHz, and 1.1 GHz). By using these methods, we successfully removed the sidebands from the NMR profiles of 13CHD2 13C-CEST experiments.","PeriodicalId":613,"journal":{"name":"Journal of Biomolecular NMR","volume":"75 2-3","pages":"133 - 142"},"PeriodicalIF":2.7,"publicationDate":"2021-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10858-021-00362-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4802300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 3

Simultaneous measurement of 1HC/N-R2′s for rapid acquisition of backbone and sidechain paramagnetic relaxation enhancements (PREs) in proteins 同时测量1HC/N-R2用于快速获取蛋白质的主链和侧链顺磁弛豫增强(PREs)

IF 2.7 3区生物学

Journal of Biomolecular NMR Pub Date : 2021-02-24 DOI: 10.1007/s10858-021-00359-9

C. Ashley Barnes, Mary R. Starich, Nico Tjandra, Pushpa Mishra

{"title":"Simultaneous measurement of 1HC/N-R2′s for rapid acquisition of backbone and sidechain paramagnetic relaxation enhancements (PREs) in proteins","authors":"C. Ashley Barnes, Mary R. Starich, Nico Tjandra, Pushpa Mishra","doi":"10.1007/s10858-021-00359-9","DOIUrl":"https://doi.org/10.1007/s10858-021-00359-9","url":null,"abstract":"Paramagnetic relaxation enhancements (PREs) are routinely used to provide long-range distance restraints for the determination of protein structures, to resolve protein dynamics, ligand–protein binding sites, and lowly populated species, using Nuclear Magnetic Resonance Spectroscopy (NMR). Here, we propose a simultaneous 1H-15?N, 1H-13C SESAME based pulse scheme for the rapid acquisition of 1HC/N-R2 relaxation rates for the determination of backbone and sidechain PREs of proteins. The 1HN-R2 rates from the traditional and our approach on Ubiquitin (UBQ) are well correlated (R2?=?0.99), revealing their potential to be used quantitatively. Comparison of the S57C UBQ calculated and experimental PREs provided backbone and side chain Q factors of 0.23 and 0.24, respectively, well-fitted to the UBQ NMR structure, showing that our approach can be used to acquire accurate PRE rates from the functionally important sites of proteins but in at least half the time as traditional methods.","PeriodicalId":613,"journal":{"name":"Journal of Biomolecular NMR","volume":"75 2-3","pages":"109 - 118"},"PeriodicalIF":2.7,"publicationDate":"2021-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10858-021-00359-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4928532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Protein in-cell NMR spectroscopy at 1.2 GHz 1.2 GHz的细胞内蛋白质核磁共振光谱

IF 2.7 3区生物学

Journal of Biomolecular NMR Pub Date : 2021-02-12 DOI: 10.1007/s10858-021-00358-w

Enrico Luchinat, Letizia Barbieri, Matteo Cremonini, Lucia Banci

引用次数: 33

A simple and cost-effective protocol for high-yield expression of deuterated and selectively isoleucine/leucine/valine methyl protonated proteins in Escherichia coli grown in shaker flasks 一种在摇瓶中培养的大肠杆菌中高效表达氘化和选择性异亮氨酸/亮氨酸/缬氨酸甲基质子化蛋白的简单且经济高效的方案

IF 2.7 3区生物学

Journal of Biomolecular NMR Pub Date : 2021-02-04 DOI: 10.1007/s10858-021-00357-x

Mengli Cai, Ying Huang, John Lloyd, Robert Craigie, G. Marius Clore

引用次数: 6