Progress in Nuclear Magnetic Resonance Spectroscopy最新文献

{"title":"Solvent paramagnetic relaxation enhancement as a versatile method for studying structure and dynamics of biomolecular systems","authors":"Aneta J. Lenard ,&nbsp;Frans A.A. Mulder ,&nbsp;Tobias Madl","doi":"10.1016/j.pnmrs.2022.09.001","DOIUrl":"10.1016/j.pnmrs.2022.09.001","url":null,"abstract":"<div><p>Solvent paramagnetic relaxation enhancement (sPRE) is a versatile nuclear magnetic resonance (NMR)-based method that allows characterization of the structure and dynamics of biomolecular systems through providing quantitative experimental information on solvent accessibility of NMR-active nuclei. Addition of soluble paramagnetic probes to the solution of a biomolecule leads to paramagnetic relaxation enhancement in a concentration-dependent manner. Here we review recent progress in the sPRE-based characterization of structural and dynamic properties of biomolecules and their complexes, and aim to deliver a comprehensive illustration of a growing number of applications of the method to various biological systems. We discuss the physical principles of sPRE measurements and provide an overview of available co-solute paramagnetic probes. We then explore how sPRE, in combination with complementary biophysical techniques, can further advance biomolecular structure determination, identification of interaction surfaces within protein complexes, and probing of conformational changes and low-population transient states, as well as deliver insights into weak, nonspecific, and transient interactions between proteins and co-solutes. In addition, we present examples of how the incorporation of solvent paramagnetic probes can improve the sensitivity of NMR experiments and discuss the prospects of applying sPRE to NMR metabolomics, drug discovery, and the study of intrinsically disordered proteins.</p></div>","PeriodicalId":20740,"journal":{"name":"Progress in Nuclear Magnetic Resonance Spectroscopy","volume":"132 ","pages":"Pages 113-139"},"PeriodicalIF":6.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0079656522000243/pdfft?md5=7028c91758875c28c201333a67024172&pid=1-s2.0-S0079656522000243-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10789954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Field and magic angle spinning frequency dependence of proton resonances in rotating solids","authors":"Kai Xue ,&nbsp;Riddhiman Sarkar ,&nbsp;Zdeněk Tošner ,&nbsp;Bernd Reif","doi":"10.1016/j.pnmrs.2022.04.001","DOIUrl":"10.1016/j.pnmrs.2022.04.001","url":null,"abstract":"<div><p>Proton detection in solid state NMR is continuously developing and allows one to gain new insights in structural biology. Overall, this progress is a result of the synergy between hardware development, new NMR methodology and new isotope labeling strategies, to name a few factors. Even though current developments are rapid, it is worthwhile to summarize what can currently be achieved employing proton detection in biological solids. We illustrate this by analysing the signal-to-noise ratio (SNR) for spectra obtained for a microcrystalline α-spectrin SH3 domain protein sample by (i) employing different degrees of chemical dilution to replace protons by incorporating deuterons in different sites, by (ii) variation of the magic angle spinning (MAS) frequencies between 20 and 110 kHz, and by (iii) variation of the static magnetic field B₀. The experimental SNR values are validated with numerical simulations employing up to 9 proton spins. Although in reality a protein would contain far more than 9 protons, in a deuterated environment this is a sufficient number to achieve satisfactory simulations consistent with the experimental data. The key results of this analysis are (i) with current hardware, deuteration is still necessary to record spectra of optimum quality; (ii) 13CH3 isotopomers for methyl groups yield the best SNR when MAS frequencies above 100 kHz are available; and (iii) sensitivity increases with a factor beyond B0 3/2 with the static magnetic field due to a transition of proton-proton dipolar interactions from a strong to a weak coupling limit.</p></div>","PeriodicalId":20740,"journal":{"name":"Progress in Nuclear Magnetic Resonance Spectroscopy","volume":"130 ","pages":"Pages 47-61"},"PeriodicalIF":6.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10499171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc finger structure determination by NMR: Why zinc fingers can be a handful","authors":"David Neuhaus","doi":"10.1016/j.pnmrs.2022.07.001","DOIUrl":"10.1016/j.pnmrs.2022.07.001","url":null,"abstract":"<div><p>Zinc fingers can be loosely defined as protein domains containing one or more tetrahedrally-co-ordinated zinc ions whose role is to stabilise the structure rather than to be involved in enzymatic chemistry; such zinc ions are often referred to as “structural zincs”. Although structural zincs can occur in proteins of any size, they assume particular significance for very small protein domains, where they are often essential for maintaining a folded state. Such small structures, that sometimes have only marginal stability, can present particular difficulties in terms of sample preparation, handling and structure determination, and early on they gained a reputation for being resistant to crystallisation. As a result, NMR has played a more prominent role in structural studies of zinc finger proteins than it has for many other types of proteins. This review will present an overview of the particular issues that arise for structure determination of zinc fingers by NMR, and ways in which these may be addressed.</p></div>","PeriodicalId":20740,"journal":{"name":"Progress in Nuclear Magnetic Resonance Spectroscopy","volume":"130 ","pages":"Pages 62-105"},"PeriodicalIF":6.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9319989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrafast 2D NMR for the analysis of complex mixtures","authors":"Célia Lhoste,&nbsp;Benjamin Lorandel,&nbsp;Clément Praud,&nbsp;Achille Marchand,&nbsp;Rituraj Mishra,&nbsp;Arnab Dey,&nbsp;Aurélie Bernard,&nbsp;Jean-Nicolas Dumez,&nbsp;Patrick Giraudeau","doi":"10.1016/j.pnmrs.2022.01.002","DOIUrl":"10.1016/j.pnmrs.2022.01.002","url":null,"abstract":"<div><p>2D NMR is extensively used in many different fields, and its potential for the study of complex biochemical or chemical mixtures has been widely demonstrated. 2D NMR gives the ability to resolve peaks that overlap in 1D spectra, while providing both structural and quantitative information. However, complex mixtures are often analysed in situations where the data acquisition time is a crucial limitation, due to an ongoing chemical reaction or a moving sample from a hyphenated technique, or to the high-throughput requirement associated with large sample collections. Among the great diversity of available fast 2D methods, ultrafast (or single-scan) 2D NMR is probably the most general and versatile approach for complex mixture analysis. Indeed, ultrafast NMR has undergone an impressive number of methodological developments that have helped turn it into an efficient analytical tool, and numerous applications to the analysis of mixtures have been reported. This review first summarizes the main concepts, features and practical limitations of ultrafast 2D NMR, as well as the methodological developments that improved its analytical potential. Then, a detailed description of the main applications of ultrafast 2D NMR to mixture analysis is given. The two major application fields of ultrafast 2D NMR are first covered, <em>i.e.</em>, reaction/process monitoring and metabolomics. Then, the potential of ultrafast 2D NMR for the analysis of hyperpolarized mixtures is described, as well as recent developments in oriented media. This review focuses on high-resolution liquid-state 2D experiments (including benchtop NMR) that include at least one spectroscopic dimension (<em>i.e.,</em> 2D spectroscopy and DOSY) but does not cover in depth applications without spectral resolution and/or in inhomogeneous fields.</p></div>","PeriodicalId":20740,"journal":{"name":"Progress in Nuclear Magnetic Resonance Spectroscopy","volume":"130 ","pages":"Pages 1-46"},"PeriodicalIF":6.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0079656522000085/pdfft?md5=03d00d36c6b266638756fdd0e5cc2875&pid=1-s2.0-S0079656522000085-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10807276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in NMR spectroscopy of ionic liquids","authors":"Krishnan Damodaran","doi":"10.1016/j.pnmrs.2021.12.001","DOIUrl":"10.1016/j.pnmrs.2021.12.001","url":null,"abstract":"<div><p>This review presents recent developments in the application of NMR spectroscopic techniques in the study of ionic liquids. NMR has been the primary tool not only for the structural characterization of ionic liquids, but also for the study of dynamics. The presence of a host of NMR active nuclei in ionic liquids permits widespread use of multinuclear NMR experiments. Chemical shifts and multinuclear coupling constants are used routinely for the structure elucidation of ionic liquids and of products formed by their covalent interactions with other materials. Also, the availability of a multitude of NMR techniques has facilitated the study of dynamical processes in them. These include the use of NOESY to study inter-ionic interactions, pulsed-field gradient techniques for probing transport properties, and relaxation measurements to elucidate rotational dynamics. This review will focus on the application of each of these techniques to investigate ionic liquids.</p></div>","PeriodicalId":20740,"journal":{"name":"Progress in Nuclear Magnetic Resonance Spectroscopy","volume":"129 ","pages":"Pages 1-27"},"PeriodicalIF":6.1,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48386312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic analysis by NMR spectroscopy: A users guide","authors":"Yael Ben-Tal ,&nbsp;Patrick J. Boaler ,&nbsp;Harvey J.A. Dale ,&nbsp;Ruth E. Dooley ,&nbsp;Nicole A. Fohn ,&nbsp;Yuan Gao ,&nbsp;Andrés García-Domínguez ,&nbsp;Katie M. Grant ,&nbsp;Andrew M.R. Hall ,&nbsp;Hannah L.D. Hayes ,&nbsp;Maciej M. Kucharski ,&nbsp;Ran Wei ,&nbsp;Guy C. Lloyd-Jones","doi":"10.1016/j.pnmrs.2022.01.001","DOIUrl":"10.1016/j.pnmrs.2022.01.001","url":null,"abstract":"<div><p>A ‘principles and practice’ tutorial-style review of the application of solution-phase NMR in the analysis of the mechanisms of homogeneous organic and organometallic reactions and processes. This review of 345 references summarises why solution-phase NMR spectroscopy is uniquely effective in such studies, allowing non-destructive, quantitative analysis of a wide range of nuclei common to organic and organometallic reactions, providing exquisite structural detail, and using instrumentation that is routinely available in most chemistry research facilities. The review is in two parts. The first comprises an introduction to general techniques and equipment, and guidelines for their selection and application. Topics include practical aspects of the reaction itself, reaction monitoring techniques, NMR data acquisition and processing, analysis of temporal concentration data, NMR titrations, DOSY, and the use of isotopes. The second part comprises a series of 15 Case Studies, each selected to illustrate specific techniques and approaches discussed in the first part, including <em>in situ</em> NMR (^1/2H, ^10/11B, ¹³C, ¹⁵N, ¹⁹F, ²⁹Si, ³¹P), kinetic and equilibrium isotope effects, isotope entrainment, isotope shifts, isotopes at natural abundance, scalar coupling, kinetic analysis (VTNA, RPKA, simulation, steady-state), stopped-flow NMR, flow NMR, rapid injection NMR, pure shift NMR, dynamic nuclear polarisation, ¹H/¹⁹F DOSY NMR, and <em>in situ</em> illumination NMR.</p></div>","PeriodicalId":20740,"journal":{"name":"Progress in Nuclear Magnetic Resonance Spectroscopy","volume":"129 ","pages":"Pages 28-106"},"PeriodicalIF":6.1,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0079656522000073/pdfft?md5=003305bf719d499bc2c2229f1de75307&pid=1-s2.0-S0079656522000073-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42554230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMR methods for exploring ‘dark’ states in ligand binding and protein-protein interactions","authors":"Vitali Tugarinov,&nbsp;Alberto Ceccon,&nbsp;G. Marius Clore","doi":"10.1016/j.pnmrs.2021.10.001","DOIUrl":"10.1016/j.pnmrs.2021.10.001","url":null,"abstract":"<div><p>A survey, primarily based on work in the authors’ laboratory during the last 10 years, is provided of recent developments in NMR studies of exchange processes involving protein–ligand and protein–protein interactions. We start with a brief overview of the theoretical background of Dark state Exchange Saturation Transfer (DEST) and lifetime line-broadening (Δ<em>R</em>₂) NMR methodology. Some limitations of the DEST/Δ<em>R</em>₂ methodology in applications to molecular systems with intermediate molecular weights are discussed, along with the means of overcoming these limitations with the help of closely related exchange NMR techniques, such as the measurements of Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion, exchange-induced chemical shifts or rapidly-relaxing components of relaxation decays. Some theoretical underpinnings of the quantitative description of global dynamics of proteins on the surface of very high molecular weight particles (nanoparticles) are discussed. Subsequently, several applications of DEST/Δ<em>R</em>₂ methodology are described from a methodological perspective with an emphasis on providing examples of how kinetic and relaxation parameters for exchanging systems can be reliably extracted from NMR data for each particular model of exchange. Among exchanging systems that are not associated with high molecular weight species, we describe several exchange NMR-based studies that focus on kinetic modelling of transient pre-nucleation oligomerization of huntingtin peptides that precedes aggregation and fibril formation.</p></div>","PeriodicalId":20740,"journal":{"name":"Progress in Nuclear Magnetic Resonance Spectroscopy","volume":"128 ","pages":"Pages 1-24"},"PeriodicalIF":6.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10602973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergies between Hyperpolarized NMR and Microfluidics: A Review","authors":"James Eills ,&nbsp;William Hale ,&nbsp;Marcel Utz","doi":"10.1016/j.pnmrs.2021.09.001","DOIUrl":"10.1016/j.pnmrs.2021.09.001","url":null,"abstract":"<div><p>Hyperpolarized nuclear magnetic resonance and lab-on-a-chip microfluidics are two dynamic, but until recently quite distinct, fields of research. Recent developments in both areas increased their synergistic overlap. By microfluidic integration, many complex experimental steps can be brought together onto a single platform. Microfluidic devices are therefore increasingly finding applications in medical diagnostics, forensic analysis, and biomedical research. In particular, they provide novel and powerful ways to culture cells, cell aggregates, and even functional models of entire organs. Nuclear magnetic resonance is a non-invasive, high-resolution spectroscopic technique which allows real-time process monitoring with chemical specificity. It is ideally suited for observing metabolic and other biological and chemical processes in microfluidic systems. However, its intrinsically low sensitivity has limited its application. Recent advances in nuclear hyperpolarization techniques may change this: under special circumstances, it is possible to enhance NMR signals by up to 5 orders of magnitude, which dramatically extends the utility of NMR in the context of microfluidic systems. Hyperpolarization requires complex chemical and/or physical manipulations, which in turn may benefit from microfluidic implementation. In fact, many hyperpolarization methodologies rely on processes that are more efficient at the micro-scale, such as molecular diffusion, penetration of electromagnetic radiation into a sample, or restricted molecular mobility on a surface. In this review we examine the confluence between the fields of hyperpolarization-enhanced NMR and microfluidics, and assess how these areas of research have mutually benefited one another, and will continue to do so.</p></div>","PeriodicalId":20740,"journal":{"name":"Progress in Nuclear Magnetic Resonance Spectroscopy","volume":"128 ","pages":"Pages 44-69"},"PeriodicalIF":6.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45425374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magic angle spinning NMR of G protein-coupled receptors","authors":"Bianca Chandler,&nbsp;Lauren Todd,&nbsp;Steven O. Smith","doi":"10.1016/j.pnmrs.2021.10.002","DOIUrl":"10.1016/j.pnmrs.2021.10.002","url":null,"abstract":"<div><p>G protein-coupled receptors (GPCRs) have a simple seven transmembrane helix architecture which has evolved to recognize a diverse number of chemical signals. The more than 800 GPCRs encoded in the human genome function as receptors for vision, smell and taste, and mediate key physiological processes. Consequently, these receptors are a major target for pharmaceuticals. Protein crystallography and electron cryo-microscopy have provided high resolution structures of many GPCRs in both active and inactive conformations. However, these structures have not sparked a surge in rational drug design, in part because GPCRs are inherently dynamic and the structural changes induced by ligand or drug binding to stabilize inactive or active conformations are often subtle rearrangements in packing or hydrogen-bonding interactions. NMR spectroscopy provides a sensitive probe of local structure and dynamics at specific sites within these receptors as well as global changes in receptor structure and dynamics. These methods can also capture intermediate states and conformations with low populations that provide insights into the activation pathways. We review the use of solid-state magic angle spinning NMR to address the structure and activation mechanisms of GPCRs. The focus is on the large and diverse class A family of receptors. We highlight three specific class A GPCRs in order to illustrate how solid-state, as well as solution-state, NMR spectroscopy can answer questions in the field involving how different GPCR classes and subfamilies are activated by their associated ligands, and how small molecule drugs can modulate GPCR activation.</p></div>","PeriodicalId":20740,"journal":{"name":"Progress in Nuclear Magnetic Resonance Spectroscopy","volume":"128 ","pages":"Pages 25-43"},"PeriodicalIF":6.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55215890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Floquet theory in magnetic resonance: Formalism and applications","authors":"Konstantin L. Ivanov ,&nbsp;Kaustubh R. Mote ,&nbsp;Matthias Ernst ,&nbsp;Asif Equbal ,&nbsp;Perunthiruthy K. Madhu","doi":"10.1016/j.pnmrs.2021.05.002","DOIUrl":"10.1016/j.pnmrs.2021.05.002","url":null,"abstract":"<div><p>Floquet theory is an elegant mathematical formalism originally developed to solve time-dependent differential equations. Besides other fields, it has found applications in optical spectroscopy and nuclear magnetic resonance (NMR). This review attempts to give a perspective of the Floquet formalism as applied in NMR and shows how it allows one to solve various problems with a focus on solid-state NMR. We include both matrix- and operator-based approaches. We discuss different problems where the Hamiltonian changes with time in a periodic way. Such situations occur, for example, in solid-state NMR experiments where the time dependence of the Hamiltonian originates either from magic-angle spinning or from the application of amplitude- or phase-modulated radiofrequency fields, or from both. Specific cases include multiple-quantum and multiple-frequency excitation schemes. In all these cases, Floquet analysis allows one to define an effective Hamiltonian and, moreover, to treat cases that cannot be described by the more popularly used and simpler-looking average Hamiltonian theory based on the Magnus expansion. An important example is given by spin dynamics originating from multiple-quantum phenomena (level crossings). We show that the Floquet formalism is a very general approach for solving diverse problems in spectroscopy.</p></div>","PeriodicalId":20740,"journal":{"name":"Progress in Nuclear Magnetic Resonance Spectroscopy","volume":"126 ","pages":"Pages 17-58"},"PeriodicalIF":6.1,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pnmrs.2021.05.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39795720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}