Conformational Dynamics of Minimal Elastin‐Like Polypeptides: The Role of Proline Revealed by Molecular Dynamics and Nuclear Magnetic Resonance

Previous molecular dynamics studies of the elastin‐like peptide (ELP) GVG(VPGVG) predict that this ELP undergoes a conformational transition from an open to a more compact closed state upon an increase in temperature. These structural changes occurring in this minimal elastin model at the so‐called inverse temperature transition (ITT), which takes place when elastin is heated to temperatures of about 20–40 ^oC, are investigated further in this work by means of a combined theoretical and experimental approach. To do this, additional extensive classical molecular dynamics (MD) simulations of the capped octapeptide are carried out, analyzed, and compared to data obtained from homonuclear magnetic resonance (NMR) spectroscopy of the same octapeptide. Moreover, in the previous simulations, the proline residue in the ELP is found to act as a hinge, thereby allowing for the large‐amplitude opening and closing conformational motion of the ITT. To explore the role of proline in such elastin repeating units, a point mutant (P5I), which replaces the proline residue with an isoleucine residue, is also investigated using the aforementioned theoretical and experimental techniques. The results show that the site‐directed mutation completely alters the properties of this ELP, thus confirming the importance of the highly conserved proline residue in the ITT. Furthermore, a correlation between the two different methods employed is seen. Both methods predict the mutant ELP to be present in an unstructured form and the wild type ELP to have a β‐turn‐like structure. Finally, the role of the peptidyl cis to trans isomerization of the proline hinge is assessed in detail.     

Fourier Transform Nuclear Magnetic Resonance Spectroscopy of Commercial Polysiloxanes

Abstract

Multinuclear Fourier transform nmr spectroscopy is shown to be a potentially useful technique for the evaluation of commercial polysiloxanes. H, ²⁹Si: and ¹³C nmr spectra are reported of the precursor solutions for RTV silicones. The ¹³C show the increased presence of an unidentified material in unacceptable lots of one of the two precursor solutions.     

脯氨酸类N-酰胺衍生物的核磁共振研究

脯氨酸类衍生物结构独特,鲜有报道利用核磁共振（nuclear magnetic resonance,NMR）技术对氨基酸的手性进行鉴别.利用多种NMR技术:1H NMR、1H-1H同核位移相关谱（1H-1H COSY）、1H-1H质子全相关谱（1H-1H TOCSY）、1H-1H核Overhauser效应谱（1H-1H NOESY）、13C NMR、无畸变的极化转移增强法（DEPT135°）、1H-13C检出1H的异核单量子相干（1H-13C HSQC）和1H-13C检出1H的异核多键相关（1H-13C HMBC）,对脯氨酸类N-酰胺衍生物两种构象异构体的1H和13C NMR进行了全归属,确定了室温下在二甲基亚砜（DMSO）中L型和D型的顺反异构体以相同的比例同时存在.     

HMGB1–Carbenoxolone Interactions: Dynamics Insights from Combined Nuclear Magnetic Resonance and Molecular Dynamics

The interplay of protein dynamics and molecular recognition is of fundamental importance in biological processes. Atomic‐resolution insights into these phenomena may provide new opportunities for drug discovery. Herein, we have combined NMR relaxation experiments and residual dipolar coupling (RDC) measurements with molecular dynamics (MD) simulations to study the effects of the anti‐inflammatory drug carbenoxolone (CBNX) on the conformational properties and on the internal dynamics of a subdomain (box A) of high‐mobility group B protein (HMGB1). ¹⁵N relaxation data show that CBNX binding enhances the fast pico‐ to nanosecond motions of a loop and partially removes the internal motional anisotropy of the first two helices of box A. Dipolar wave analysis of amide RDC data shows that ligand binding induces helical distortions. In parallel, increased mobility of the loop upon ligand binding is highlighted by the essential dynamics analysis (EDA) of MD simulations. Moreover, simulations detect two possible orientations for CBNX, which induces two possible conformations of helix H3, one being similar to the free form and the second one causing a partial helical distortion. Finally, we introduce a new approach for the analysis of the internal coordination of protein residues that is consistent with experimental data and allows us to pinpoint which substructures of box A are dynamically affected by CBNX. The observations reported here may be useful for understanding the role of protein dynamics in binding at atomic resolution.     

核磁共振技术(NMR)在组合化学中的应用

对科学产生最大影响的分析方法是核磁共振技术(NMR),它被广泛用于许多领域.本文结合作者的研究结果评述了NMR在组合化学中的应用,着重于NMR在固相合成的应用、液态NMR和NMR在高通量筛选中的应用.     

Accelerated Nuclear Magnetic Resonance Spectroscopy with Deep Learning

Nuclear magnetic resonance (NMR) spectroscopy serves as an indispensable tool in chemistry and biology but often suffers from long experimental times. We present a proof-of-concept of the application of deep learning and neural networks for high-quality, reliable, and very fast NMR spectra reconstruction from limited experimental data. We show that the neural network training can be achieved using solely synthetic NMR signals, which lifts the prohibiting demand for a large volume of realistic training data usually required for a deep learning approach.     

Billion‐Fold Enhancement in Sensitivity of Nuclear Magnetic Resonance Spectroscopy for Magnesium Ions in Solution

β‐nuclear magnetic resonance (NMR) spectroscopy is highly sensitive compared to conventional NMR spectroscopy, and may be applied for several elements across the periodic table. β‐NMR has previously been successfully applied in the fields of nuclear and solid‐state physics. In this work, β‐NMR is applied, for the first time, to record an NMR spectrum for a species in solution. ³¹Mg β‐NMR spectra are measured for as few as 10⁷ magnesium ions in ionic liquid (EMIM‐Ac) within minutes, as a prototypical test case. Resonances are observed at 3882.9 and 3887.2 kHz in an external field of 0.3 T. The key achievement of the current work is to demonstrate that β‐NMR is applicable for the analysis of species in solution, and thus represents a novel spectroscopic technique for use in general chemistry and potentially in biochemistry.     

Accelerated Nuclear Magnetic Resonance Spectroscopy with Deep Learning

Nuclear magnetic resonance (NMR) spectroscopy serves as an indispensable tool in chemistry and biology but often suffers from long experimental times. We present a proof‐of‐concept of the application of deep learning and neural networks for high‐quality, reliable, and very fast NMR spectra reconstruction from limited experimental data. We show that the neural network training can be achieved using solely synthetic NMR signals, which lifts the prohibiting demand for a large volume of realistic training data usually required for a deep learning approach.     

Review and Prospect: Deep Learning in Nuclear Magnetic Resonance Spectroscopy

Since the concept of deep learning (DL) was formally proposed in 2006, it has had a major impact on academic research and industry. Nowadays, DL provides an unprecedented way to analyze and process data with demonstrated great results in computer vision, medical imaging, natural language processing, and so forth. Herein, applications of DL in NMR spectroscopy are summarized, and a perspective for DL as an entirely new approach that is likely to transform NMR spectroscopy into a much more efficient and powerful technique in chemistry and life sciences is outlined.     

Cos-7细胞胞内pH的31 P核磁共振测定

生物细胞内pH的测定对于细胞内代谢、游离离子及离子通道的研究有重要的意义,而且一些酶的活性也与细胞内pH密切相关。猴的肾细胞cos-7细胞常用于外源基因的转染表达,研究这一细胞株细胞内的pH,可为基因转染提供可靠的依据。本文采用^31P核磁共振对cos-7细胞胞内的pH进行了分析测定。     

高场核磁共振波谱在多糖结构研究中的应用

随着高场核磁共振波谱（ＮＭＲ）技术飞速发展,它在多糖的结构研究中发挥着日益重要的作用,不仅对共 结构,而且对于多糖在溶液中或固体状态下的构象以及动力学特性,ＮＭＲ分析也是最有力的工具。本文综述了高场ＮＭＲ技术在分析多糖结构方面的应用。     

Nuclear Magnetic Resonance in Solid-State Chemistry

Various problems of solid-state chemistry can be solved by spectroscopic investigation of the nuclear magnetic resonance (NMR and NQR methods). This progress report presents a survey of the nature of the interactions in the crystal that underlie such measurements, of the observations in the spectrum, and of the information obtainable from it. The field of application of the methods covers both static and dynamic properties of solids.     

细胞内游离离子及离子通道的核磁共振研究

生物细胞内游离离子及离：子通道(Ca^2 、Mg^2 、Na^ 、K^ 以及Na^ ／Ca^2 和Na^ ／Li^ 交换等)在生理病理过程中起着重要作用。用于这些方面研究的生物核磁共振方法主要包括有：^31PNMR、^19NMR、^7Li NMR及^23Na NMR等。^31P NMR主要用于对细胞内小分子代谢物、pH及游离Mg^2 的分析测定；^19F NMR是利用氟代指示剂间接地测定细胞内游离Mg^2 和Ca^2 的浓度，进而对钙镁离子通道进行分析研究；^7Li NMR、^23Na NMR等方法分别用于研究Li^ 、Na^ ／Li^ 交换、Mg^2 ／Li^ 交换、Na^ 及K^ 等。为了更好地理解和阐释细胞内离子的调控机制，本文对近几年核磁共振技术在这些方面的应用进行了综述。     

Carbon-13 Nuclear Magnetic Resonance Spectroscopy Study of the Glucose Stress of Human Lenses

The sorbitol theory in diabetic cataractogenesis was based on sorbitol accumulation under glucose stress. Sorbitol accumulation was examined by ¹³C nuclear magnetic resonance spectroscopy (NMR) for the first time in matched human lenses incubated in 5.5 mM and 35.5 mM C-1 ¹³C-enriched glucose up to 28 hours. The results showed that sorbitol and lactate in human tens can be detected at 35.5 mM, but not in 5.5 mM glucose solution. The glycolysis metabolic pathway of human lenses may be quite different from that of animals. The accumulation of metabolites can be traced and quantified by the intensities of ¹³C NMR peaks. Therefore, ¹³C NMR spectroscopy can be used as a valuable tool to investigate human lens carbohydrate metabolism non-interventionally.     

核磁共振成像(NMRI)在非医学领域中的应用

对核磁共振成像(NMRI)与核磁共振(NMR)波谱进行了概括性的比较.重点介绍了当前NMRI在非医学领域最新应用的进展情况,同时对NMRI的发展也做了回顾与展望.     

核磁共振定量法测定利培酮含量

采用氢核磁共振定量法和氟核磁共振定量法测定利培酮含量。氢核磁共振定量法以利培酮δ7.29~7.35处质子峰为定量峰,马来酸δ6.02处为内标峰,在恒温300 K,采样时间4.0 s,弛豫延迟时间15 s,扫描次数为32次条件下采集氢谱。氟核磁共振定量法以4-溴-2-氟-乙酰苯胺为内标,在恒温300 K,谱宽12 500.0 Hz,中心频率-43 662.7 Hz下采集氟谱。测试结果显示,利培酮氢核磁共振定量法和氟核磁共振定量法的含量测定结果基本与质量平衡法的结果一致。因此,核磁共振法可用于利培酮绝对含量的测定,具有快速、简单、准确的优势。