Laccase/caffeic acid-catalyzed crosslinking coupled with galactomannan alters the conformational structure of ovalbumin and alleviates Th2-mediated allergic asthma

Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are inadequate.In this study,we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid(Lac/CA)-catalyzed crosslinking in conjunction with galactomannan(Man).The formation of high molecular weight crosslinked polymers and the Ig G-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting.The study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface hydrophobicity.Gastrointestinal digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid(SGF)and simulated intestinal fluid(SIF).Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines(interleukin(IL)-4,IL-5,and IL-13),and upregulated IFN-γand IL-10 expression.Stimulation of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers(CD80 and CD86)and MHC class II molecules,and suppressed the expression levels of proinflammatory cytokines.The knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.

Illuminating β-arrestin conformational dynamics by fluorine NMR

In a recent paper, solution-state ^(19)F NMR spectroscopy was used to probe the conformational dynamics of β-arrestin-1, an essential adaptor and signaling component of the G-protein couple receptor (GPCR) signaling pathway. This work reveals a highly complex conformational energy landscape of β-arrestin-1, and illuminates the molecular mechanism of the membrane phosphoinositide PIP2-induced β-arrestin-1 activation at residue level.(https://doi.org/10.1038/s41467-023-43694-1).

Recent advances in protein conformation sampling by combining machine learning with molecular simulation

The rapid advancement and broad application of machine learning(ML)have driven a groundbreaking revolution in computational biology.One of the most cutting-edge and important applications of ML is its integration with molecular simulations to improve the sampling efficiency of the vast conformational space of large biomolecules.This review focuses on recent studies that utilize ML-based techniques in the exploration of protein conformational landscape.We first highlight the recent development of ML-aided enhanced sampling methods,including heuristic algorithms and neural networks that are designed to refine the selection of reaction coordinates for the construction of bias potential,or facilitate the exploration of the unsampled region of the energy landscape.Further,we review the development of autoencoder based methods that combine molecular simulations and deep learning to expand the search for protein conformations.Lastly,we discuss the cutting-edge methodologies for the one-shot generation of protein conformations with precise Boltzmann weights.Collectively,this review demonstrates the promising potential of machine learning in revolutionizing our insight into the complex conformational ensembles of proteins.

Electric Field-induced Conformational Transition of Bovine Serum Albumin from α-helix to β-sheet

The irreversible conformational transition of bovine serum albumin (BSA) from α-helix to β-sheet, induced by electric field near the electrode surface, was monitored by circular dichroism (CD) with a long optical path thin layer cell (LOPTLC).

Spatial Conformation Analysis of Urban Complex as Wanda Plaza in Chengdu City of China

Through analyzing the overall spatial conformation of Wanda Plaza in Chengdu City, a typical urban complex, the whole space was classified into external plaza space, internal business space and its connection with external space. Characteristics of such an urban complex and its contained correlation were elaborated from the perspectives of spatial conformation, organization technique and connotation. And it was proposed that the urban complex should be regarded as an organic whole with dynamic changes and mutually-influenced units, attractiveness of external space and cohesion of internal space, so as to define the organization techniques influencing regional spatial conformation and also practical significance of these techniques.

APM3 Molecular Orbital Study on the Conformational Equilibrium of Cyclohexane upon α-Cyclodextrin Inclusion Complexation

用PM3分子轨道方法研究了α -环糊精的包合作用对环己烷构象平衡的影响。发现α -环糊精的包合作用可以改变环己烷的构象平衡。计算结果表明 ,虽然环己烷的椅式构象比船式构象稳定 1 8.5kJ·mol-1,但在α-环糊精的包合物中 ,船式环己烷包合物比椅式环己烷包合物稳定4.4kJ·mol-1。因此 ,超分子体系中客体分子的构象平衡不能简单地从其游离态的构象平衡外推得到 。

Study on the Equivalent Conformation of Retinoids

N-(4-Carboxy-phenyl)-3,5-di-t-butyl-4-hydroxy-benzamide (2) possesses structural prerequisite for cell differentiation inducing activity, which constitutes the therapeutic basis of all trans retinoic acid (ATRA) and analogues for the treatment of cancer and dermatosis. In addition to the similarity of the disposition of functional groups with ATRA, 2 shows a conformational equivalence to ATRA in terms of molecular shape, size, as well as the spatial arrangement of functional groups. However, the N methylated compound (3) is devoid of the activity. It owes the biological behavior to the conformational difference, because of the steric interference between N methyl group and the hydrogen atom of a phenyl ring. X ray crystallography, UV, and NMR were performed to investigate the difference.

基于改进Conformer的新闻领域端到端语音识别

目前,开源的中文语音识别数据集大多面向通用领域,缺少面向新闻领域的开源语音识别语料库,因此该文构建了面向新闻领域的中文语音识别数据集CH_NEWS_ASR,并使用ESPNET-0.9.6框架的RNN、Transformer和Conformer等模型对数据集的有效性进行了验证,实验表明,该文所构建的语料在最好的模型上CER为4.8%,SER为39.4%。由于新闻联播主持人说话语速相对较快,该文构建的数据集文本平均长度为28个字符,是Aishell_1数据集文本平均长度的2倍;且以往的研究中训练目标函数通常为基于字或词水平,缺乏明确的句子水平关系,因此该文提出了一个句子层级的一致性模块,与Conformer模型结合,直接减少源语音和目标文本的表示差异,在开源的Aishell_1数据集上其CER降低0.4%,SER降低2%;在CH_NEWS_ASR数据集上其CER降低0.9%,SER降低3%,实验结果表明,该方法在不增加模型参数量的前提下能有效提升语音识别的质量。

A Novel Conformation Investigation on Newly Synthesized Compound of Diethyl Puerarin-7-yl Phosphate

A novel compound, diethyl puerarin-7-yl phosphate, was synthesized through a simplified Atheron-Todd reaction for the first time. The structure of this compound was elucidated by IR, ESI-MS and NMR. Two conformations of the compound were testified by 2D NMR （HSQC and HMBC） and dynamic NMR. Furthermore, we carried out the conformational analysis using chemical calculation by the Gaussian 03. Finally, we obtained two preferred conformations and energy values.

Modeling and analysis of Schistosoma Argonaute protein molecular spatial conformation

Objective:To analyze the amino acid sequence composition,secondary structure,the spatial conformation of its domain and other characteristics of Argonaute protein.Methods:Bioinformatics tools and the internet server were used.Firstly,the amino acid sequence composition features of the Argonaute protein were analyzed,and the phylogenetic tree was constructed.Secondly,Argonaute protein's distribution of secondary structure and its physicochemical properties were predicted.Lastly,the protein functional expression form of the domain group was established through the Phyre-based analysis on the spatial conformation of Argonaute protein domains.Results:593 amino acids were encoded by Argonaute protein,the phylogenetic tree was constructed,and Argonaute protein's distribution of secondary structure and its physicochemical properties were obtained through analysis.In addition,the functional expression form which comprised the N-terminal PAZ domain and C-terminal Piwi domain for the Argonaute protein was obtained with Phyre.Conclusions:The information relationship between the structure and function of the Argonaute protein can be initially established with bioinformatics tools and the internet server,and this provides the theoretical basis for further clarifying the function of Schistosoma Argonaute protein.

Improved Brassica rapa reference genome by single-molecule sequencing and chromosome conformation capture technologies

Brassica rapa comprises several important cultivated vegetables and oil crops.Current reference genome assemblies of Brassica rapa are quite fragmented and not highly contiguous,thereby limiting extensive genetic and genomic analyses.Here,we report an improved assembly of the B.rapa genome(v3.0)using single-molecule sequencing,optical mapping,and chromosome conformation capture technologies(Hi-C).Relative to the previous reference genomes,our assembly features a contig N50 size of 1.45 Mb,representing a~30-fold improvement.We also identified a new event that occurred in the B.rapa genome~1.2 million years ago,when a long terminal repeat retrotransposon(LTR-RT)expanded.Further analysis refined the relationship of genome blocks and accurately located the centromeres in the B.rapa genome.The B.rapa genome v3.0 will serve as an important community resource for future genetic and genomic studies in B.rapa.This resource will facilitate breeding efforts in B.rapa,as well as comparative genomic analysis with other Brassica species.

EFFECTS OF METAL IONS ON THE CONFORMATIONAL CHANGES OF DNA

DNA takes on multi-different conformations such as A-, B-, C-, D- and Z-form. These conformations can transit to one another when DNA deposited in some metal ions solutions or when changing the concentrations of the same metal ions. Here, several major conformational transitions of DNA induced by metal ions under different environment were introduced and the mechanism of the interaction of metal ions with DNA was discuss in detail.

Studies on the Molecular Chain Conformation Stability of Aminated Konjac Glucomannan

Konjac glucomannan （KGM） was aminated by 2-chloroethyl-amine （CEA） as reagent so as to study the influence of concentration of CEA （based on the amount of KGM）, concentration of NaOH, reaction time and temperature on the extent of amination. And the molecular simulation technology was adopted to analyze the conformation stability of aminate （AKGM）. The results indicate that when the amount of CEA is higher, the extent of amination is higher. The optimum concentration of NaOH, reaction time and temperature are 10% NaOH, 70 ℃ and 45 rain, respectively. IR shows KGM is successfully aminated. The conformation of AKGM is in a random clew-like shape.

Effects of different valences of cerium ion on conformation of Horseradish Peroxidase

Our previous studies demonstrated that Ce^4＋could induce reactive oxygen species （ROS） burst as a signal to promote pacilitaxel biosynthesis in suspension cultured Taxus cuspidate cells. To further understand the mechanism of cerium ions inducing ROS burst, circular dichroism （CD）, synchronous fluorescence, and electron paramagnetic resonance （EPR） were used to detect them inducing conformational change of horseradish peroxidase （HRP）. Horseradish peroxidase activity was reduced by 78% by 0.1 mmol/L Ce^4＋, whereas it was only reduced by 28% by 0.1 mmol/L Ce^3＋. Circular dichroism spectra showed that the percentage of transition from helical content and other structure to β strands and flturns was 23.1 when induced by Ce^4＋, whereas it was only 13.2 when induced by Ce^3＋. In synchronous fluorescence spectra, Ce^4＋ led to red shift and intensity-elevation of tryptophan fluorescence emission maximum, whereas in the case of Ce^3＋, the results were a contrast to the above. Furthermore, g factor （gx and gy） in electron paramagnetic resonance （EPR） induced by Ce^4＋ and Ce^3＋ was significantly different. These results indicated that the different valence of cerium ion induced various conformations of HRP, and Ce^4＋ was more effective than Ce^3＋. This suggested that Ce^4＋ affected the burst of ROS through changing the conformation of oxidoreductase.

Binding of Pyrene to Different Molecular Weight Fractions of Dissolved Organic Matter:Effects of Chemical Composition and Steric Conformation

The binding constant（KDOM） of pyrene onto different molecular weight（Mw） fractions of a dissolved organic matter（DOM） extract from an estuarine sediment was measured via a fluorescence quenching method,and the possible binding mechanisms were discussed.The influence of water chemical parameters on pyrene binding was studied to elucidate the effects of DOM steric conformation.DOM fraction with larger M w（14000） showed a greater KDOM（2.02×10 5） than that with smaller Mw did,and the KDOMs were 1.16×105 and 1.13×105 for the fractions with M w of 1000―14000 and 1000,respectively.The K DOM s of different M w DOM fractions were correlated positively with the atomic ratio of C/H and absorbance at 280 nm;while a negative correlation existed between K DOM and（O＋C）/N（atomic ratio）,and K DOM and O-containing groups.These correlations indicate the positive influence of aromatic structure and the negative effect of polarity on DOM binding capacity.Infrared spectroscopy revealed that specific interactions existed between pyrene and the DOM fraction with larger M W besides hydrophobic partition,i.e.,NH-π interaction in DOM moiety（1000―14000） and π-π electron donor acceptor（EDA） forces in DOM moiety（14000）.KDOM varied in a complex pattern with increasing cation concentration and pH,which could be explained by the change in DOM steric conformation.Formed aggregates favored the lipophilic partition of pyrene.However,the accessibility to some interior binding sites became low when the aggregate was too large,leading to a reduced KDOM.

Theoretical Studies on the Conformation of mono-6-O-p-nitrobenzoyl-β-cyclodextrin in Aqueous Solution

The conformation of mono-6-O-p-nitrobenzoyl-β-cyclodextrin was studied with B3LYP/6-311g**//PM3 calculations in vacuum and in water solution. It was concluded that the p-nitrobenzoyl group of the molecule should be located above the primary hydroxyls of the cyclodextrin instead of being completely enclosed by the cavity. It was proposed that the behavior might be caused by the requirement of a cis ester bond in the self-included conformation of the molecule.

Separation of Salbutamol by Nano-baskets of Calix[4]arene Bearing Sulfonyl-carboxamides in Partial-cone Conformation

Salbutamol,which increases the muscle mass and decreases the adipose tissue,is misused as nutrient repartitioning agent in the livestock.The novelty of this work is the determination of salbutamol in the livestock meat via new bonded-phases bearing eight derivatives of p-tert-calix[4]arene in partial-cone conformation.The new synthesized bonded-phases were characterized and optimized.The bonding interactions of solute and stationary-phases were examined and the main interactions were reported.The salbutamol levels in six samples of livestock meat were analyzed and the results reveal that for the best bonded-phases,the limit of detection（LOD） and limit of quantitation（LOQ） were 0.02 and 0.06 μg/mL,respectively.

Non-thermal effects of 0.1 THz radiation on intestinal alkaline phosphatase activity and conformation

Alkaline phosphatase(ALP) plays an integral role in the metabolism of liver and development of the skeleton in humans. To date, the interactions between different-duration terahertz(THz) radiation and ALP activities, as well as the influence mechanism are still unclear. In this study, using the para-nitro-phenyl-phosphate(p NPP) method, we detect changes in ALP activities during 40-minute THz radiation(0.1 THz, 13 m W/cm^2). It is found that the activity of ALP decreases in the first 25 min, and subsequently increases in the later 15 min. Compared with the activity of ALP being heated, the results suggest that short-term terahertz radiation induces a decrease in enzyme activity through the non-thermal mechanism. In order to explore the non-thermal effects of THz radiation on ALP, we focus on the impacts of 0.1 THz radiation for 20 min on the activity of ALP in different concentrations. The results reveal that the activity of ALP decreases significantly after exposure to THz radiation. In addition, it could be deduced from fluorescence, ultraviolet-visible(UV-vis), and THz spectra results that THz radiation has induced changes in ALP structures. Our study unlocks non-thermal interactions between THz radiation and ALP, as well as suggests that THz spectroscopy is a promising technique to distinguish ALP structures.

Gas Phase Conformations of Tetrapeptide Glycine-Phenylalanine- Glycine-Glycine

Systematic search of the potential energy surface of tetrapeptide glycine-phenylalanine- glycine-glycine （GFGG） in gas phase is conducted by a combination of PM3, HF and BHandHLYP methods. The conformational search method is described in detail. The relative electronic energies, zero point vibrational energies, dipole moments, rotational constants, vertical ionization energies and the temperature dependent conformational distributions for a number of important conformers are obtained. The structural characteristics of these conformers are analyzed and it is found that the entropic effect is a dominating factor in determining the relative stabilities of the conformers. The measurements of dipole moments and some characteristic IR mode are shown to be effective approaches to verify the theoreti- cal prediction. The structures of the low energy GFGG conformers are also analyzed in their connection with the secondary structures of proteins. Similarity between the local structures of low energy GFGG conformers and the α-helix is discussed and many β- and γ-turn local structures in GFGG conformers are found.

Chain Conformation and Local Rigidity of Soluble Polyimides(II):Isomerized Polyimides in THF

Two soluble isomerized polyimides（PIs） synthesized from 2,2＇-bis（3,4-dicarboxyphenyl）hexafluoropropane dianhydride（6FDA） with either 2,2＇-dimethylbenzidine（2,2＇-DMB） or 3,3＇-DMB were investigated by means of size-exclusion chromatography coupled with multi-angle laser light scattering,a viscometer and a refractive index detector in tetrahydrofuran（THF） with tetrabutylammonium bromide（TBAB） at 35 ℃.The corresponding parameters related to conformations α and ν,evaluated from the scaling relationships [η]=K η M α and R g =K g M ν,respectively,were 0.66±0.01 and 0.55±0.02 for poly（6FDA/3,3＇-DMB）,and 0.67±0.01 and 0.56±0.01 for poly（6FDA/2,2＇-DMB）,indicating a random coil conformation for both the samples in this mobile system.The persistence length l p and shift factor M L（relative molecular weight per unit contour length） were estimated from the relationship between intrinsic viscosity and molecular weight for the wormlike cylinder model proposed by Bohdanecky.Both l p and M L showed that the two PIs in THF are flexible chains and exhibit some local rigidity to some extent.