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.

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.

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).

In situ kinetics and flocs conformation studies of kaolinite flocculated by Chi-g-CPAM

This study presents a comparative study of the flocculation behavior of kaolinite induced by chitosan-graft-poly(acrylamide-dimethyl diallyl ammonium chloride)(Chi-g-CPAM) and a commercial cationic polyacrylamide(CPAM).The flocculation behaviour was characterised in terms of both flocculation kinetics and the corresponding morphology changes during flocculation.Both Chi-g-CPAM and CPAM were grafted from silica wafers by means of atom transfer radical polymerization(ATRP).The quartz crystal microbalance with dissipation(QCM-D) tests were conducted.The equilibrium time flocculated by Chi-g-CPAM was found to be 0.46 times as that of CPAM,together with a larger total mass of kaolinite layer.The flocculation behaviour by Chi-g-CPAM can be well captured by a pseudo-first-order model.In contrast,the presence of CPAM leads to a more complex kinetics.A relatively larger fitting slope(0.4663) was obtained at the initial stage but the fitting slope droped to 0.2026 after 800 min,indicating a densification process caused by CPAM.The flocculation kinetics of CPAM can be captured by the Elovich model for the inital stage but the combination of pseudo-first-order and pseudo-second-order models for the latter stages,which can be attributed to the long chain of CPAM.With a dosage of 75 g/t,the settling test with Chi-g-CPAM exhibits the same turbidity in the supernatant but a smaller layer thickness of the settlement compared to CPAM.The study enables a better understanding of the flocculation behavior and contributes to the development of efficient flocculants in mineral processing and tailings treatment.

Conformations and Metal Ion Affinities of Glutamine Binding with Alkali and Alkaline Earth Metal Cations： an ab initio Study

Conformations and reaction energetics are important for understanding the interactions be- tween biomolecules and metal ions. In this work, we report a systematic ab initio study on the conformations and metal ion affinities of glutamine （Gln） binding with alkali and alkaline earth metal ions. An efficient and reliable method of searching low energy conformations of metalated Gln is proposed and applied to the complexes of Gln.Gln.M^＋/＋＋（M＋/＋＋=Li^＋、Na^＋、K^＋、Rb^＋、Cs^＋、Be^＋＋、Mg^＋＋、Ca^＋＋、Sr^＋＋ and Ba^＋＋）.. In addition to all conformers known in literatures, many new important conformations are located, demonstrating the power of the new method and the necessity of the conformational search performed here. The metal coordination modes, relative energies, dipole moments, and equilibrium distributions of all important conformations of Gln.M^＋/＋＋ are calculated by the methods of B3LYP, BHandHLYP, and MP2. IR spectra and metalation enthalpies and free energies are also presented and compared with the available experiments. The results form an extensive database for systematic examination of the metalation properties of Gln.

CALCULATION OF CONFORMATIONAL ENTROPY AND FREE ENERGY OF POLYSILANE CHAIN

The conformational entropy S and free energy F were calculated by exact enumeration of polysilane chain up to 23 segments with excluded volume (EV) and long-range van der Waals (VW) interaction. A nonlinear relation between SEV+VW and chain length n was found though S-EV was found to vary linearly with n. We found that the second-order transition temperature of polysilane chain with VW interaction increases with the increase of chain length, while that of polysilane chain without VW interaction is chain length independent. Moreover, the free energies FEV+VW and F-EV are both linearly related with n, and FEV+VW < F-EV for all temperatures.

Study on the Conformation of Cyclodecapeptide Loloatin C with Obvious Antibiotic Activity

The conformation of cyclodecapeptide loloatin C with obvious antibiotic activity has been investigated in 2,2,2-trifluoroethanol/sodium acetate buffer solution and then characterized by FT-IR, CD and NMR spectrum. The results of FT-IR show that there exists β-strand or β-turn secondary structure in the molecule. According to the CD spectrum, the helical turn is dominant but the β-turn structure also exists. Conformation of the whole molecule is probably a helical β-turn. The chemical shifts and coupling constants prove the existence of a β-structure in the regions of Val1, Orn2 and Leu3. NOESY data and temperature gradients of amide protons suggest that the molecular conformation is a dumbbell-like structure with the waist located between ornithyl (position 2) and D-phenylalanyl (position 7) and β-turn on both ends.

The stable planar conformation of the γ-butyrolactone ring in solution

The conformations ofγ-butyrolactone ring in solution were deduced on the basis of ~1H NMR spectra of geminal protons of the butyrolactone ring.A series of optically pure(Z)-(-)-4-(1 -alkoxyl-1 -carbalkoxy-methylene)-5(R)[(1R)-menthyloxy]-γ-butyr-olactones with a stable planar conformation of γ-butyrolactone ring were found.

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.

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.

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.

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.

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.

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.

Computational Exploration of Conformations of Glycine-Arginine and a Deduced Model on Global Minimum Configurations of Dipeptides in Gas Phase

An extensive computational study on the conformations of gaseous dipeptide glycine- arginine, GlyArg, has been performed. A large number of trail structures were generated by systematically sampling the potential energy surface （PES） of OlyArg. The trial structures were successively optimized with the methods of PM3, HF/3-21G＊, BHandHLYP/6-31G＊ and BHandHLYP/6-311＋＋G＊＊ in order to reliably find the low energy conformations. The eonformational energies were finally determined with the methods of BHandHLYP, cam- B3LYP, B97D, and MP2 using the basis set of 6-311＋＋G（3df,3pd）. The results establish firmly that gaseous GlyArg exists primarily in its canonical form, in sharp contrast with ArgGly that adopts the zwitterionic form. Important data such as the rotational constants, dipole moments, vertical ionization energies, temperature distributions and IR spectra of the low energy conformers are represented for the understanding of the future experiments. Moreover, considering the global minima of all amino acids and many dipeptides, combined with the hydrophobicities of amino acids, a model predicting whether the global minimum configuration of a dipeptide is canonical or zwitterionic is developed.

Protein Conformational Change Based on a Two-dimensional Generalized Langevin Equation

A two-dimensional generalized Langevin equation is proposed to describe the protein conformational change, compatible to the electron transfer process governed by atomic packing density model. We assume a fractional Gaussian noise and a white noise through bond and through space coordinates respectively, and introduce the coupling effect coming from both fluctuations and equilibrium variances. The general expressions for autocorrelation functions of distance fluctuation and fluorescence lifetime variation are derived, based on which the exact conformational change dynamics can be evaluated with the aid of numerical Laplace inversion technique. We explicitly elaborate the short time and long time approximations. The relationship between the two-diraensional description and the one-dimensional theory is also discussed.

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.

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.

Protein conformation and electric attraction adsorption mechanisms on anodized magnesium alloy by molecular dynamics simulations

Protein adsorption preferentially occurs and significantly affects the physicochemical reactions once the biodegradable magnesium alloys as bone replacements have been implanted. To date, interactions mechanisms between Mg implants and proteins remain unclear at a molecular level. Thereby, a combination of molecular dynamic(MD) simulations and experimental exploration is used to investigate the adsorption behavior and conformational change of bovine serum albumin(BSA), a representative protein of blood plasma, upon the surface of microarc oxidation(MAO) coated Mg alloy AZ31. The influences of absorbed proteins on the cytocompatibility of MAO coating are evaluated by virtue of cytotoxicity assay. Results indicate that the negatively charged O atoms(BSA) exhibit strong interaction with Mg^(2+) ions of Mg(OH)_(2), revealing that BSA molecules are ionically adsorbed on the AZ31 surface. Interestingly, MD simulation reveals that MAO coating demonstrates superior ability to capture BSA molecules during the process of adsorption owing to strong electric attraction between the negatively charged O atoms in BSA molecules with Mg atoms of MgO in MAO coating. Moreover, the α-helix part of absorbed BSA molecules on AZ31 substrate and MAO coating markedly decreases with an increase in β-sheet, β-turn and unordered contents, which is attributed to the reduction in the number of hydrogen bonds in BSA molecules. Furthermore, the adsorbed BSA molecules improve the cytocompatibility of MAO coating since the positively charged-NH_(3)^(+) group and β-sheet content of absorbed BSA molecules mediate the cell adhesion by interacting with the negatively charged cell membrane.

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.