The assembly behaviors of two low-symmetric carboxylic acid molecules(50-(6-carboxynaphthalen-2-yl)-[1,10:30,100-triphenyl]-3,400,5-tricarboxylic acid(CTTA)and 30,50-bis(6-carboxynaphthalen-2-yl)-[1,10-biphenyl]-3,5-d...The assembly behaviors of two low-symmetric carboxylic acid molecules(50-(6-carboxynaphthalen-2-yl)-[1,10:30,100-triphenyl]-3,400,5-tricarboxylic acid(CTTA)and 30,50-bis(6-carboxynaphthalen-2-yl)-[1,10-biphenyl]-3,5-dicarboxylic acid(BCBDA))containing naphthalene rings on graphite surfaces have been investigated using scanning tunneling microscopy(STM).The transformation of nanostructures induced by the second components(EDA and PEBP-C4)have been also examined.Both CTTA and BCBDA molecules self-assemble at the 1-heptanoic acid(HA)/HOPG interface,forming porous network structures.The dimer represents the most elementary building unit due to the formation of double hydrogen bonds.Moreover,the flipping of naphthalene ring results in the isomerization of BCBDA molecule.The introduction of carboxylic acid derivative EDA disrupts the dimer,which subsequently undergoes a structural conformation to form a novel porous structure.Furthermore,upon the addition of pyridine derivative PEBP-C4,N–H⋯O hydrogen bonds are the dominant forces driving the three coassembled structures.We have also conducted density functional theory(DFT)calculations to determine the molecular conformation and analyze the mechanisms underlying the formation of nanostructures.展开更多
To regulate the sodium chloride content in Jinhua ham,the impact of NaCl on the activity and conformation of cathepsin B was investigated using spectroscopy and computational methods.The results showed that the activi...To regulate the sodium chloride content in Jinhua ham,the impact of NaCl on the activity and conformation of cathepsin B was investigated using spectroscopy and computational methods.The results showed that the activity of cathepsin B decreased with an increase in Na^(+)cation content and temperature.Additionally,decreasedα-helix content and increasedβ-sheet content were observed.The increase in sulfhydryl group content was attributed to the breaking of original disulfide bonds in the molecular structure or the release of embedded groups.Furthermore,the surface hydrophobicity gradually declined,which was consistent with the analysis of endogenous fluorescence spectroscopy.At the molecular level,the number of hydrogen bonds formed in NaCl-treated samples decreased,and the interactions between the hydrogen bonding were less powerful,which caused instability in the binding of the protein and substrate.The conformation of cathepsin B accurately characterized its activity,and the structural changes had a macroscopic effect on the decrease in protease activity.展开更多
Dynamic adaptability is a key feature in biological macromolecules,enabling selective binding and catalysis[1].From DNA supercoiling to enzyme conformational changes,biological systems have evolved intricate ways to d...Dynamic adaptability is a key feature in biological macromolecules,enabling selective binding and catalysis[1].From DNA supercoiling to enzyme conformational changes,biological systems have evolved intricate ways to dynamically adjust their structures to accommodate functional needs.Mimicking this adaptability in synthetic systems is an ongoing challenge in supramolecular chemistry.展开更多
Gaining insights into charge transport related to conformational changes and ion transport in valinomycin(VM)is crucial for understanding the underlying physiological processes and advancing ion carrier applications.O...Gaining insights into charge transport related to conformational changes and ion transport in valinomycin(VM)is crucial for understanding the underlying physiological processes and advancing ion carrier applications.Observing these processes in single molecules provides deeper insights and precision than those obtained through conventional ensemble measurements.Herein,we employed a single-molecule conductance measurement method based on the scanning tunneling microscopy break-junction(STM-BJ)to measure the charge transport of individual VM molecules in both non-polar and polar solvents,as well as when mediated by K^(+)ions.Single-molecule conductance measurements revealed that the bracelet and propeller-type conformations of VM in both non-polar and polar solvents significantly affect its conductance.In polar solvents,the propeller-type conformation of VM demonstrated a well-defined conductance signature,single-molecule rectification feature,and through-space transmission mechanism.Specifically,the introduction of K^(+)ions in polar solvents induced a conformational transition from the propeller-type to the bracelet-type form,facilitating K^(+)binding recognition.These observations were further supported by density functional theory combined with non-equilibrium Green’s function calculations.This study enhanced the fundamental understanding of the electronic transport mechanisms in VM and valinomycin-K^(+)molecular junctions,offering insights into VM ionophores and promoting supramolecular sensing applications.展开更多
Understanding the conformational characteristics of polymers is key to elucidating their physical properties.Cyclic polymers,defined by their closed-loop structures,inherently differ from linear polymers possessing di...Understanding the conformational characteristics of polymers is key to elucidating their physical properties.Cyclic polymers,defined by their closed-loop structures,inherently differ from linear polymers possessing distinct chain ends.Despite these structural differences,both types of polymers exhibit locally random-walk-like conformations,making it challenging to detect subtle spatial variations using conventional methods.In this study,we address this challenge by integrating molecular dynamics simulations with point cloud neural networks to analyze the spatial conformations of cyclic and linear polymers.By utilizing the Dynamic Graph CNN(DGCNN)model,we classify polymer conformations based on the 3D coordinates of monomers,capturing local and global topological differences without considering chain connectivity sequentiality.Our findings reveal that the optimal local structural feature unit size scales linearly with molecular weight,aligning with theoretical predictions.Additionally,interpretability techniques such as Grad-CAM and SHAP identify significant conformational differences:cyclic polymers tend to form prolate ellipsoid shapes with pronounced elongation along the major axis,while linear polymers show elongated ends with more spherical centers.These findings reveal subtle yet critical differences in local conformations between cyclic and linear polymers that were previously difficult to discern,providing deeper insights into polymer structure-property relationships and offering guidance for future polymer science advancements.展开更多
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 v...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.展开更多
Polyelectrolyte solutions are more variable than uncharged macromolecule due to electrical interaction between charged molecules and surrounding counterions.Therefore,the subject of polyelectrolyte solutions has attra...Polyelectrolyte solutions are more variable than uncharged macromolecule due to electrical interaction between charged molecules and surrounding counterions.Therefore,the subject of polyelectrolyte solutions has attracted a wide range of interests in both basic and applied research,and has also been extensively explored.However,the understanding of the molecular dynamics and conformation of polyelectrolytes in solution remains to be deepened,and universal consensus on some key issues have not been reached.Many methods have contributed to solving the above problems in different ways,including dielectric relaxation spectroscopy(DRS).In this perspective,we briefly reviewed the history of dielectric spectroscopic research on polyelectrolyte solution,with emphasis on summarizing our efforts.In particular,we expound the characteristics of DRS and its ability to obtain the internal information of the system of interest.Finally,we evaluate the advantages and limitations of the dielectric method and discussed future prospects of this field.展开更多
Achieving selectivity in cell penetrating peptide(CPP)design is crucial to mitigate systemic toxicity and enable precise targeting based on distinct cellular phenotypes.Herein,we designed an amphiphilic peptide,L17Yp,...Achieving selectivity in cell penetrating peptide(CPP)design is crucial to mitigate systemic toxicity and enable precise targeting based on distinct cellular phenotypes.Herein,we designed an amphiphilic peptide,L17Yp,by incorporating phosphorylated tyrosine into natural occurring M-lycotoxin peptide,known for its potent membrane-lytic activity.This strategic modification induced a conformational shift,as confirmed by circular dichroism spectroscopy,transitioning it from its bioactiveα-helix conformation to an inactive random coli configuration,effectively shielding its membrane-penetrating capacity.Upon exposure to alkaline phosphatase,L17Yp undergoes enzymatic dephosphorylation,prompting a conformational shift that restores its membrane-transduction capabilities.This unique property hold promises for selective drug delivery.This work introduces an enzymatic approach for targeted perturbation of the cell membrane,offering promising prospects for precise drug delivery applications.展开更多
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...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.展开更多
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 ...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).展开更多
基金financially supported by the National Natural Science Foundation of China(No.22272039)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB36000000)+1 种基金the Youth Program of the Liaoning Education Department(No.LJKQZ20222280)the Jilin Chinese Academy of Sciences-Yanshen Technology Co.,Ltd.
文摘The assembly behaviors of two low-symmetric carboxylic acid molecules(50-(6-carboxynaphthalen-2-yl)-[1,10:30,100-triphenyl]-3,400,5-tricarboxylic acid(CTTA)and 30,50-bis(6-carboxynaphthalen-2-yl)-[1,10-biphenyl]-3,5-dicarboxylic acid(BCBDA))containing naphthalene rings on graphite surfaces have been investigated using scanning tunneling microscopy(STM).The transformation of nanostructures induced by the second components(EDA and PEBP-C4)have been also examined.Both CTTA and BCBDA molecules self-assemble at the 1-heptanoic acid(HA)/HOPG interface,forming porous network structures.The dimer represents the most elementary building unit due to the formation of double hydrogen bonds.Moreover,the flipping of naphthalene ring results in the isomerization of BCBDA molecule.The introduction of carboxylic acid derivative EDA disrupts the dimer,which subsequently undergoes a structural conformation to form a novel porous structure.Furthermore,upon the addition of pyridine derivative PEBP-C4,N–H⋯O hydrogen bonds are the dominant forces driving the three coassembled structures.We have also conducted density functional theory(DFT)calculations to determine the molecular conformation and analyze the mechanisms underlying the formation of nanostructures.
基金supported by the National Natural Science Foundation of China(31972097)Jiangsu Key Research and Development Plan(Modern Agriculture)(BE2020302)+1 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(24KJB550003)2024 Huaiyin Institute of Technology Talent Recruitment Research Startup Fund Project(Z301B24521)。
文摘To regulate the sodium chloride content in Jinhua ham,the impact of NaCl on the activity and conformation of cathepsin B was investigated using spectroscopy and computational methods.The results showed that the activity of cathepsin B decreased with an increase in Na^(+)cation content and temperature.Additionally,decreasedα-helix content and increasedβ-sheet content were observed.The increase in sulfhydryl group content was attributed to the breaking of original disulfide bonds in the molecular structure or the release of embedded groups.Furthermore,the surface hydrophobicity gradually declined,which was consistent with the analysis of endogenous fluorescence spectroscopy.At the molecular level,the number of hydrogen bonds formed in NaCl-treated samples decreased,and the interactions between the hydrogen bonding were less powerful,which caused instability in the binding of the protein and substrate.The conformation of cathepsin B accurately characterized its activity,and the structural changes had a macroscopic effect on the decrease in protease activity.
基金the Natural Science Foundation of China(No.22301131)the Natural Science Foundation of Jiangsu Province(Nos.BK20220781,BK20240679)the National Key Research and Development Program of China(No.2024YFB3815700)are greatly acknowledged.
文摘Dynamic adaptability is a key feature in biological macromolecules,enabling selective binding and catalysis[1].From DNA supercoiling to enzyme conformational changes,biological systems have evolved intricate ways to dynamically adjust their structures to accommodate functional needs.Mimicking this adaptability in synthetic systems is an ongoing challenge in supramolecular chemistry.
基金supported by the National Key R&D Program of China(Nos.2022YFB3204402,2020YFA0714703 and 2022YFC2205003)the National Natural Science Foundation of China(No.22204135)+2 种基金Hunan Provincial Natural Science Foundation of China(No.2023JJ40619)the Education Department of Hunan Province(No.23A0114)the Science and Technology Innovation Program of Hunan Province(No.2022RC3027)。
文摘Gaining insights into charge transport related to conformational changes and ion transport in valinomycin(VM)is crucial for understanding the underlying physiological processes and advancing ion carrier applications.Observing these processes in single molecules provides deeper insights and precision than those obtained through conventional ensemble measurements.Herein,we employed a single-molecule conductance measurement method based on the scanning tunneling microscopy break-junction(STM-BJ)to measure the charge transport of individual VM molecules in both non-polar and polar solvents,as well as when mediated by K^(+)ions.Single-molecule conductance measurements revealed that the bracelet and propeller-type conformations of VM in both non-polar and polar solvents significantly affect its conductance.In polar solvents,the propeller-type conformation of VM demonstrated a well-defined conductance signature,single-molecule rectification feature,and through-space transmission mechanism.Specifically,the introduction of K^(+)ions in polar solvents induced a conformational transition from the propeller-type to the bracelet-type form,facilitating K^(+)binding recognition.These observations were further supported by density functional theory combined with non-equilibrium Green’s function calculations.This study enhanced the fundamental understanding of the electronic transport mechanisms in VM and valinomycin-K^(+)molecular junctions,offering insights into VM ionophores and promoting supramolecular sensing applications.
基金the National Key R&D Program of China(No.2022YFB3707303)National Natural Science Foundation of China(No.52293471)。
文摘Understanding the conformational characteristics of polymers is key to elucidating their physical properties.Cyclic polymers,defined by their closed-loop structures,inherently differ from linear polymers possessing distinct chain ends.Despite these structural differences,both types of polymers exhibit locally random-walk-like conformations,making it challenging to detect subtle spatial variations using conventional methods.In this study,we address this challenge by integrating molecular dynamics simulations with point cloud neural networks to analyze the spatial conformations of cyclic and linear polymers.By utilizing the Dynamic Graph CNN(DGCNN)model,we classify polymer conformations based on the 3D coordinates of monomers,capturing local and global topological differences without considering chain connectivity sequentiality.Our findings reveal that the optimal local structural feature unit size scales linearly with molecular weight,aligning with theoretical predictions.Additionally,interpretability techniques such as Grad-CAM and SHAP identify significant conformational differences:cyclic polymers tend to form prolate ellipsoid shapes with pronounced elongation along the major axis,while linear polymers show elongated ends with more spherical centers.These findings reveal subtle yet critical differences in local conformations between cyclic and linear polymers that were previously difficult to discern,providing deeper insights into polymer structure-property relationships and offering guidance for future polymer science advancements.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2021B15151300042021B1515140021)+2 种基金the Scientific Research Start-up Funding of Guangdong Medical University(1026/4SG21229G)China Postdoctoral Science Foundation(2021M702781)Guangdong Medical University Post-doctoral Research Funding(2BH19006P)。
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.21673002,21473012 and 21173025).
文摘Polyelectrolyte solutions are more variable than uncharged macromolecule due to electrical interaction between charged molecules and surrounding counterions.Therefore,the subject of polyelectrolyte solutions has attracted a wide range of interests in both basic and applied research,and has also been extensively explored.However,the understanding of the molecular dynamics and conformation of polyelectrolytes in solution remains to be deepened,and universal consensus on some key issues have not been reached.Many methods have contributed to solving the above problems in different ways,including dielectric relaxation spectroscopy(DRS).In this perspective,we briefly reviewed the history of dielectric spectroscopic research on polyelectrolyte solution,with emphasis on summarizing our efforts.In particular,we expound the characteristics of DRS and its ability to obtain the internal information of the system of interest.Finally,we evaluate the advantages and limitations of the dielectric method and discussed future prospects of this field.
基金supported by the National Natural Science Foundation of China(No.21975068)Natural Science Foundation of Hunan(No.2022JJ10008)+1 种基金Science and Technology and Development Foundation of Shenzhen(No.JCYJ20210324122403010)Natural Science Foundation of Changsha(No.kq2202152)。
文摘Achieving selectivity in cell penetrating peptide(CPP)design is crucial to mitigate systemic toxicity and enable precise targeting based on distinct cellular phenotypes.Herein,we designed an amphiphilic peptide,L17Yp,by incorporating phosphorylated tyrosine into natural occurring M-lycotoxin peptide,known for its potent membrane-lytic activity.This strategic modification induced a conformational shift,as confirmed by circular dichroism spectroscopy,transitioning it from its bioactiveα-helix conformation to an inactive random coli configuration,effectively shielding its membrane-penetrating capacity.Upon exposure to alkaline phosphatase,L17Yp undergoes enzymatic dephosphorylation,prompting a conformational shift that restores its membrane-transduction capabilities.This unique property hold promises for selective drug delivery.This work introduces an enzymatic approach for targeted perturbation of the cell membrane,offering promising prospects for precise drug delivery applications.
基金Project supported by the National Key Research and Development Program of China(Grant No.2023YFF1204402)the National Natural Science Foundation of China(Grant Nos.12074079 and 12374208)+1 种基金the Natural Science Foundation of Shanghai(Grant No.22ZR1406800)the China Postdoctoral Science Foundation(Grant No.2022M720815).
文摘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.
文摘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).
