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
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
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 b...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.展开更多
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 G...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.展开更多
A full-relaxation optimization of molecule and the Dreiding force field are employed to obtain the geometry parameters and the conformational energy surfaces of meso or racemic dyad of poly(acrylic acid) (PAA) and pol...A full-relaxation optimization of molecule and the Dreiding force field are employed to obtain the geometry parameters and the conformational energy surfaces of meso or racemic dyad of poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA). Three different carbonyl-bond orientations of side-groups resulted in the differences in depth of potential wells in their energetic contours for a meso or a racemic dyad. These discrepancies are interpreted as a result of various fine structures corresponding to grid search conformations as well as thereby different interactions. The analysis on the most stable conformations of PMAA confirmed that the ester groups are nearly perpendicular to the plane defined by the two adjacent skeletal bonds but may possibly change their relative orientations to meet the requirement of lower energy during the conformational state transition. For each polymer, two global energy maps of a meso and a racemic dyad were finally constructed from the superposition of energy data for the three kinds of side-group orientations by the Boltzmann factors. From an ensemble average, the proposed scheme with three rotational isomeric states (RIS) allowed us to access the experimentally unperturbed dimensions of PAA chain via the configurational statistical mechanics. Although the calculation was based on the short-range, local interactions, it was interested to note that the experimental characteristic ratios just fell within the range calculated for atactic chains.展开更多
The DNA conformational transition depends on both the DNA sequences and environment such as solvent as well as electrolyte in the solution. This paper uses the AMBER8 package to investigate the electrolyte concentrati...The DNA conformational transition depends on both the DNA sequences and environment such as solvent as well as electrolyte in the solution. This paper uses the AMBER8 package to investigate the electrolyte concentration influence on the dynamics of the A→B conformational transition of DNA duplex d（CGCGAATTCGCG）2. The results from the restrained molecular dynamics （MD） simulations indicate that the total energies of the systems for A-DNA are always higher than those for B-DNA, and that the A→B conformational transition in aqueous NaCl solution is a downhill process. The results from the unrestrained MD simulations, as judged by the average distance between the C5＇ atoms （average helical rise per ten base pair）, show that the concentrated NaC1 solution slows down the A→B conformational transition. This observation can be well understood by analyses of the difference between the counterion distributions around A-DNA and B-DNA.展开更多
ATP-binding cassette exporters transport many substrates out of cellular membranes via alternating between inward-facing and outward-facing conformations. Despite extensive research efforts over the past decades, unde...ATP-binding cassette exporters transport many substrates out of cellular membranes via alternating between inward-facing and outward-facing conformations. Despite extensive research efforts over the past decades, understanding of the molecular mechanism remains elusive. As these large-scale conformational movements are global and collective, we have previously performed extensive coarse-grained molecular dynamics simulations of the potential of mean force along the conformational transition pathway [J. Phys. Chem. B 119, 1295(2015)]. However, the occluded conformational state, in which both the internal and external gate are closed, was not determined in the calculated free energy profile. In this work, we extend the above methods to the calculation of the free energy profile along the reaction coordinate, d1-d2, which are the COM distances between the two sides of the internal(d1)and the external gate(d2). The potential of mean force is thus obtained to identify the transition pathway, along which several outward-facing, inward-facing, and occluded state structures are predicted in good agreement with structural experiments. Our coarse-grained molecular dynamics free-energy simulations demonstrate that the internal gate is closed before the external gate is open during the inward-facing to outward-facing transition and vice versa during the inward-facing to outward-facing transition. Our results capture the unidirectional feature of substrate translocation via the exporter, which is functionally important in biology. This finding is different from the previous result, in which both the internal and external gates are open reported in an X-ray experiment [Proc. Natl. Acad. Sci. USA 104,19005(2007)]. Our study sheds light on the molecular mechanism of the state transitions in an ATP-binding cassette exporter.展开更多
The title complex is widely used as an efficient key component of Ziegler-Natta catalyst for stereospecific polymerization of dienes to produce synthetic rubbers. However, the quantitative structure-activity relations...The title complex is widely used as an efficient key component of Ziegler-Natta catalyst for stereospecific polymerization of dienes to produce synthetic rubbers. However, the quantitative structure-activity relationship（QSAR） of this kind of complexes is still not clear mainly due to the difficulties to obtain their geometric molecular structures through laboratory experiments. An alternative solution is the quantum chemistry calculation in which the comformational population shall be determined. In this study, ten conformers of the title complex were obtained with the function of molecular dynamics conformational search in Gabedit 2.4.8, and their geometry optimization and thermodynamics calculation were made with a Sparkle/PM7 approach in MOPAC 2012. Their Gibbs free energies at 1 atm. and 298.15 K were calculated. Population of the conformers was further calculated out according to the theory of Boltzmann distribution, indicating that one of the ten conformers has a dominant population of 77.13%.展开更多
Objective:To do mapping and modeling of conformational B cell epitope regions of highly conserved and protective regions of three merozoitecandidate vaccine proteins of Plasmodium vivax(P.vivax),ie.merozoite purface p...Objective:To do mapping and modeling of conformational B cell epitope regions of highly conserved and protective regions of three merozoitecandidate vaccine proteins of Plasmodium vivax(P.vivax),ie.merozoite purface protein-1(PvMSP-1),apical membrane antigen-1 domainⅡ(PvAMA1-DⅡ)and regionⅡof the Duffy binding protein(PvDBPⅡ).and to analyze the immunogenie properties of these predicted epitopes.Methods:3-D structures of amino acid haplotypes from Sri Lanka(available in GeneBank)of PvMSP-1_(19)(n=27),PvAMA1-DⅡ(n=21)and PvDBPⅡ(n=33)were modeled.SEPPA,selected as the best online server was used for conformational epitope predictions,while prediction and moodeling of protein structuve and properties related to immunogenicity was carried out with Geno3D server.SCRATCH Protein Server,NetSurfP Server and standaloneroftware,Genious 5.4.4.Results:SEPPA revealed that regions of predicted conformational epitopes formed 4 clusters in PvMSP-I_(19),and 3 clusters each in PvAMA1-DⅡand PvDBPⅡ,all of which displayed a high degree of hydrophilicity,contained solveut exposed residues,displayed high probability of antigenicity and showed positive antigenic propensity values,that indicated high degree of immunogenicity.Conclusions:Findings of this study revealed and confirmed that different parts of the sequences of each of the conserved regions of the three selected potential vaccine candidate antigens of P.vivax are important with regard to conformational epitope prediction that warrants further laboratory experimental invertigations in in vivo animal models.展开更多
Theoretical results of normal coordinate analysis of polybenzamide performed with two conformational isomerized models, the cis trans and the all-trans conformation, have been adopted to examine a number of infrared s...Theoretical results of normal coordinate analysis of polybenzamide performed with two conformational isomerized models, the cis trans and the all-trans conformation, have been adopted to examine a number of infrared spectra of films of the polymer treated in a subsequent annealing process and a cooling process. It shows, in this investigation, that two sets of infrared spectral profiles around 1400 cm^(-1) and 900 cm^(-1) behave quite attractively. Their spectral behaviours have been correlated to the conformational defect variation in samples, and reasonably predicted by the normal coordinate calculation.展开更多
Proteins are crucial to most biological processes, such as enzymes, and in various catalytic processes a dynamic motion is required. The dynamics of protein are embodied as a conformational change, which is closely re...Proteins are crucial to most biological processes, such as enzymes, and in various catalytic processes a dynamic motion is required. The dynamics of protein are embodied as a conformational change, which is closely related to the flexibility of protein. Recently, nanopore sensors have become accepted as a low cost and high throughput method to study the features of proteins. In this article, we used a SiN nanopore device to study the flexibility of T7 RNA polymerase（RNAP） and its complex with DNA promoter. By calculating full-width at half-maximum（FWHM） of Gaussian fits to the blockade histograms, we found that T7 RNAP becomes more flexible after binding DNA promoter. Moreover, the distribution of fractional current blockade suggests that flexibility alters due to a breath-like change of the volume.展开更多
Monte-Carlo simulated annealing method (SA) was applied to the conformational analysis of flexible molecules such as peptides. The programs SAMM and SAPEP have been developed, using MM2 force field for organic molecul...Monte-Carlo simulated annealing method (SA) was applied to the conformational analysis of flexible molecules such as peptides. The programs SAMM and SAPEP have been developed, using MM2 force field for organic molecules and ECEPP/2 force field for peptides respectively.展开更多
Spider silk, relying on its exceptional mechanical properties, has attracted extensive attention throughout the world. The structure of a material can influence its mechanical properties. Investigation of the structur...Spider silk, relying on its exceptional mechanical properties, has attracted extensive attention throughout the world. The structure of a material can influence its mechanical properties. Investigation of the structure of spider silk includes amino acid composition, molecular structure, self-assembly, and crystallization, among other characteristics. Herein, the effects of concentration, time, alkali metal ions （Na^＋and K ^＋ ） and pH on the conformational transition and self-assembly of regenerated Ornithoctonus huwena spider dragline silk protein （spidroin） in water were investigated using circular dichroism （CD） and atomic force microScopy （AFM）. Spidroin concentration, time and Na ＋ ions slightly influenced the conformational transition of spidroin molecules. However, K ＋ ions and pH induced the formation of a β- sheet structure. Increasing spidroin concentration or time increased the aggregation of spidroin and enhanced the formation of nanoffiaments. K ~ ions enhanced the serf-assembly of spidroin into nanofilaments. The self-assembled nanofilaments appeared at a pH of approximately 6. 11. Both lower and higher pH induced aggregation. At a lower pH, the aggregation was composed of nanopartides, whereas higher pH induced the aggregation of nanoffiaments, likely from the synergistic effect of Na ^＋ ions and pH.展开更多
We study the properties of the ethylene glycol solutions and the conformational transitions of DNA segment in the ethylene glycol solutions by molecular dynamics simulations based on GROMACS. The hydrogen network stru...We study the properties of the ethylene glycol solutions and the conformational transitions of DNA segment in the ethylene glycol solutions by molecular dynamics simulations based on GROMACS. The hydrogen network structures of water–water and ethylene glycol–water are reinforced by ethylene glycol molecules when the concentrations of the solutions increase from 0% to 80%. As illustrated by the results, conformation of the double-stranded DNA in ethylene glycol solutions, although more compact, is similar to the structure of DNA in the aqueous solutions. In contrast, the DNA structure is an A–B hybrid state in the ethanol/water mixed solution. A fraying of terminal base-pairs is observed for the terminal cytosine. The ethylene glycol molecules preferentially form a ring structure around the phosphate groups to influence DNA conformation by hydrogen interactions, while water molecules tend to reside in the grooves. The repulsion between the negatively charged phosphate groups is screened by ethylene glycol molecules, preventing the repulsion from unwinding and extending the helix and thus making the conformation of DNA more compact.展开更多
The title compound,（E）-5-methoxy-2-（（4-methoxyphenylimino）methyl）phenol（C15H15NO3）,crystallizes in monoclinic,space group P21/c with a=9.4361（6）,b=10.6212（5）,c=12.9338（9）,β=93.064（5）o,V=1294.41（14）3...The title compound,（E）-5-methoxy-2-（（4-methoxyphenylimino）methyl）phenol（C15H15NO3）,crystallizes in monoclinic,space group P21/c with a=9.4361（6）,b=10.6212（5）,c=12.9338（9）,β=93.064（5）o,V=1294.41（14）3,Z=4,Dc=1.320 g/cm3,F（000）=544,Rint=0.116,T=296 K,μ=0.09 mm-1,the final R=0.051 and wR=0.148 for 1836 observed reflections with I2σ（I）.An extensive two-dimensional network of C–H…O hydrogen bonds and π-ring interactions are responsible for the crystal stabilization.Intermolecular hydrogen bonds and C–H…π interactions produce R22（14）,R44（30） and R44（31） rings.In addition to the molecular geometry from X-ray experiment,the molecular geometry of the title compound in the ground state has been calculated using the semi-empirical（AM1 and PM3） and density functional theory method（DFT）（B3LYP） with 6-31G（d） basis set.To determine the conformational flexibility,molecular energy profile of the title compound was obtained by semi-empirical（PM3 and AM1） and DFT/B3LYP calculations with respect to the selected degree of torsional freedom,which varied from –180° to ＋180° in a step of 10°.展开更多
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 pa...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).展开更多
Bacitracin consists of a mixture of several closely related polypeptide antibiotics produced from Bacillus licheniformis.The major component, Bacitracin A, is a cyclic dodecapeptide（Fig, 1）, which has strong bacteri...Bacitracin consists of a mixture of several closely related polypeptide antibiotics produced from Bacillus licheniformis.The major component, Bacitracin A, is a cyclic dodecapeptide（Fig, 1）, which has strong bacteriocidal effect on the G+ bacteria. The bacteriocidal activity requires the presence of divalent cations such as Zn;, As we know, the biological function of ploypeptides and proteins are closely related to their three-dimensional structure. Bacitracin A is very important for the demonstration of the coordination site of metal and the relationship between展开更多
Troponin is a thin filament-associated regulator of vertebrate striated muscle contraction. Troponin changes its structure upon Ca2+ binding to troponin C, one of the subunits of troponin, allowing myosin to interact ...Troponin is a thin filament-associated regulator of vertebrate striated muscle contraction. Troponin changes its structure upon Ca2+ binding to troponin C, one of the subunits of troponin, allowing myosin to interact with actin. We recently elucidated the molecular characteristics of the Japanese pearl oyster Pinctada fucata troponin C (Pifuc-TnC), revealing the possibilities that Pifuc-TnC and vertebrate muscle TnC play dissimilar roles in muscle contraction. Pifuc-TnC has four EF-hand motifs, but, unlike vertebrate TnC, only one (site IV) was predicted to bind Ca2+. To confirm the number of Ca2+-binding sites in Pifuc-TnC and whether Ca2+ binding induces a conformational change, we purified the full-length protein and a variant, Pifuc-TnC-E142Q (that has a mutation in the predicted Ca2+-binding site of site IV), following their expression in laboratory E. coli. Isothermal titration calorimetry demonstrated Ca2+ binding to Pifuc-TnC, whereas Pifuc-TnC-E142Q was unable to bind Ca2+, confirming that site IV is the only Ca2+-binding site in Pifuc-TnC. Pifuc-TnC eluted in a later fraction from a gel filtration column in the presence of Ca2+ compared with the condition when Ca2+ was absent. In contrast, the elution profiles of Pifuc-TnC-E142Q were equivalent in both the presence and absence of Ca2+, suggesting that Ca2+ binding to Pifuc-TnC induces a conformational change that delays its elution from the column. UV-absorption spectral analysis revealed that binding of Ca2+ to Pifuc-TnC caused an increase in absorption at a wavelength of approximately 250 nm, possibly because phenylalanine residues had been exposed on the surface of the molecule as a result of a conformational change. Differential scanning calorimetric analyses of Pifuc-TnC showed aggregation in the presence of Ca2+ in accordance with an increase of temperature, but no aggregation was seen in the absence of Ca2+. In combination, these findings suggest that Ca2+ binding to site IV induces a conformational change in Pifuc-TnC.展开更多
A series of trans-4, 5-disubstituted -γ-butyrolactones are found to assume two different envelope conformations by means of nuclear magnetic resonance spectroscopy.
Introduction Integrins are a large family of adhesion molecules broadly expressed on the surface of a wide variety of cells as heterodimers. Binding of integrins to ligands provides not only mechanical anchorage for t...Introduction Integrins are a large family of adhesion molecules broadly expressed on the surface of a wide variety of cells as heterodimers. Binding of integrins to ligands provides not only mechanical anchorage for the cell to another cell or展开更多
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.
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).
文摘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.
基金This work was supported by the National Natural Science Foundation of China （No.20973119 and No.21033008）.
文摘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.
基金This work was supported by the Youth Science Foundation of Acedemia Sinica the China Postdoctoral Science Foundation, the National Natural Science Foundation of China, and Polymer Physics Laboratory,Academia Sinica
文摘A full-relaxation optimization of molecule and the Dreiding force field are employed to obtain the geometry parameters and the conformational energy surfaces of meso or racemic dyad of poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA). Three different carbonyl-bond orientations of side-groups resulted in the differences in depth of potential wells in their energetic contours for a meso or a racemic dyad. These discrepancies are interpreted as a result of various fine structures corresponding to grid search conformations as well as thereby different interactions. The analysis on the most stable conformations of PMAA confirmed that the ester groups are nearly perpendicular to the plane defined by the two adjacent skeletal bonds but may possibly change their relative orientations to meet the requirement of lower energy during the conformational state transition. For each polymer, two global energy maps of a meso and a racemic dyad were finally constructed from the superposition of energy data for the three kinds of side-group orientations by the Boltzmann factors. From an ensemble average, the proposed scheme with three rotational isomeric states (RIS) allowed us to access the experimentally unperturbed dimensions of PAA chain via the configurational statistical mechanics. Although the calculation was based on the short-range, local interactions, it was interested to note that the experimental characteristic ratios just fell within the range calculated for atactic chains.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.20876083 and 20736003)Specialized Research Fund for the Doctorial Program of Higher Education of China(Grant No.2007003009)
文摘The DNA conformational transition depends on both the DNA sequences and environment such as solvent as well as electrolyte in the solution. This paper uses the AMBER8 package to investigate the electrolyte concentration influence on the dynamics of the A→B conformational transition of DNA duplex d（CGCGAATTCGCG）2. The results from the restrained molecular dynamics （MD） simulations indicate that the total energies of the systems for A-DNA are always higher than those for B-DNA, and that the A→B conformational transition in aqueous NaCl solution is a downhill process. The results from the unrestrained MD simulations, as judged by the average distance between the C5＇ atoms （average helical rise per ten base pair）, show that the concentrated NaC1 solution slows down the A→B conformational transition. This observation can be well understood by analyses of the difference between the counterion distributions around A-DNA and B-DNA.
基金supported by the National Natu-ral Science Foundation of China(No.21073170 and No.21273209).
文摘ATP-binding cassette exporters transport many substrates out of cellular membranes via alternating between inward-facing and outward-facing conformations. Despite extensive research efforts over the past decades, understanding of the molecular mechanism remains elusive. As these large-scale conformational movements are global and collective, we have previously performed extensive coarse-grained molecular dynamics simulations of the potential of mean force along the conformational transition pathway [J. Phys. Chem. B 119, 1295(2015)]. However, the occluded conformational state, in which both the internal and external gate are closed, was not determined in the calculated free energy profile. In this work, we extend the above methods to the calculation of the free energy profile along the reaction coordinate, d1-d2, which are the COM distances between the two sides of the internal(d1)and the external gate(d2). The potential of mean force is thus obtained to identify the transition pathway, along which several outward-facing, inward-facing, and occluded state structures are predicted in good agreement with structural experiments. Our coarse-grained molecular dynamics free-energy simulations demonstrate that the internal gate is closed before the external gate is open during the inward-facing to outward-facing transition and vice versa during the inward-facing to outward-facing transition. Our results capture the unidirectional feature of substrate translocation via the exporter, which is functionally important in biology. This finding is different from the previous result, in which both the internal and external gates are open reported in an X-ray experiment [Proc. Natl. Acad. Sci. USA 104,19005(2007)]. Our study sheds light on the molecular mechanism of the state transitions in an ATP-binding cassette exporter.
基金supported by the National Natural Science Foundation of China(No.21476119)
文摘The title complex is widely used as an efficient key component of Ziegler-Natta catalyst for stereospecific polymerization of dienes to produce synthetic rubbers. However, the quantitative structure-activity relationship（QSAR） of this kind of complexes is still not clear mainly due to the difficulties to obtain their geometric molecular structures through laboratory experiments. An alternative solution is the quantum chemistry calculation in which the comformational population shall be determined. In this study, ten conformers of the title complex were obtained with the function of molecular dynamics conformational search in Gabedit 2.4.8, and their geometry optimization and thermodynamics calculation were made with a Sparkle/PM7 approach in MOPAC 2012. Their Gibbs free energies at 1 atm. and 298.15 K were calculated. Population of the conformers was further calculated out according to the theory of Boltzmann distribution, indicating that one of the ten conformers has a dominant population of 77.13%.
文摘Objective:To do mapping and modeling of conformational B cell epitope regions of highly conserved and protective regions of three merozoitecandidate vaccine proteins of Plasmodium vivax(P.vivax),ie.merozoite purface protein-1(PvMSP-1),apical membrane antigen-1 domainⅡ(PvAMA1-DⅡ)and regionⅡof the Duffy binding protein(PvDBPⅡ).and to analyze the immunogenie properties of these predicted epitopes.Methods:3-D structures of amino acid haplotypes from Sri Lanka(available in GeneBank)of PvMSP-1_(19)(n=27),PvAMA1-DⅡ(n=21)and PvDBPⅡ(n=33)were modeled.SEPPA,selected as the best online server was used for conformational epitope predictions,while prediction and moodeling of protein structuve and properties related to immunogenicity was carried out with Geno3D server.SCRATCH Protein Server,NetSurfP Server and standaloneroftware,Genious 5.4.4.Results:SEPPA revealed that regions of predicted conformational epitopes formed 4 clusters in PvMSP-I_(19),and 3 clusters each in PvAMA1-DⅡand PvDBPⅡ,all of which displayed a high degree of hydrophilicity,contained solveut exposed residues,displayed high probability of antigenicity and showed positive antigenic propensity values,that indicated high degree of immunogenicity.Conclusions:Findings of this study revealed and confirmed that different parts of the sequences of each of the conserved regions of the three selected potential vaccine candidate antigens of P.vivax are important with regard to conformational epitope prediction that warrants further laboratory experimental invertigations in in vivo animal models.
文摘Theoretical results of normal coordinate analysis of polybenzamide performed with two conformational isomerized models, the cis trans and the all-trans conformation, have been adopted to examine a number of infrared spectra of films of the polymer treated in a subsequent annealing process and a cooling process. It shows, in this investigation, that two sets of infrared spectral profiles around 1400 cm^(-1) and 900 cm^(-1) behave quite attractively. Their spectral behaviours have been correlated to the conformational defect variation in samples, and reasonably predicted by the normal coordinate calculation.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.51622201,91733301,and 61571015)
文摘Proteins are crucial to most biological processes, such as enzymes, and in various catalytic processes a dynamic motion is required. The dynamics of protein are embodied as a conformational change, which is closely related to the flexibility of protein. Recently, nanopore sensors have become accepted as a low cost and high throughput method to study the features of proteins. In this article, we used a SiN nanopore device to study the flexibility of T7 RNA polymerase（RNAP） and its complex with DNA promoter. By calculating full-width at half-maximum（FWHM） of Gaussian fits to the blockade histograms, we found that T7 RNAP becomes more flexible after binding DNA promoter. Moreover, the distribution of fractional current blockade suggests that flexibility alters due to a breath-like change of the volume.
文摘Monte-Carlo simulated annealing method (SA) was applied to the conformational analysis of flexible molecules such as peptides. The programs SAMM and SAPEP have been developed, using MM2 force field for organic molecules and ECEPP/2 force field for peptides respectively.
基金the Priority Academic Program Development of Jiangsu Higher Education Institutions,China
文摘Spider silk, relying on its exceptional mechanical properties, has attracted extensive attention throughout the world. The structure of a material can influence its mechanical properties. Investigation of the structure of spider silk includes amino acid composition, molecular structure, self-assembly, and crystallization, among other characteristics. Herein, the effects of concentration, time, alkali metal ions （Na^＋and K ^＋ ） and pH on the conformational transition and self-assembly of regenerated Ornithoctonus huwena spider dragline silk protein （spidroin） in water were investigated using circular dichroism （CD） and atomic force microScopy （AFM）. Spidroin concentration, time and Na ＋ ions slightly influenced the conformational transition of spidroin molecules. However, K ＋ ions and pH induced the formation of a β- sheet structure. Increasing spidroin concentration or time increased the aggregation of spidroin and enhanced the formation of nanoffiaments. K ~ ions enhanced the serf-assembly of spidroin into nanofilaments. The self-assembled nanofilaments appeared at a pH of approximately 6. 11. Both lower and higher pH induced aggregation. At a lower pH, the aggregation was composed of nanopartides, whereas higher pH induced the aggregation of nanoffiaments, likely from the synergistic effect of Na ^＋ ions and pH.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11635003,11025524,and 11161130520)the National Basic Research Program of China(Grant No.2010CB832903)the European Commissions 7th Framework Programme(FP7-PEOPLE-2010-IRSES)(Grant No.269131)
文摘We study the properties of the ethylene glycol solutions and the conformational transitions of DNA segment in the ethylene glycol solutions by molecular dynamics simulations based on GROMACS. The hydrogen network structures of water–water and ethylene glycol–water are reinforced by ethylene glycol molecules when the concentrations of the solutions increase from 0% to 80%. As illustrated by the results, conformation of the double-stranded DNA in ethylene glycol solutions, although more compact, is similar to the structure of DNA in the aqueous solutions. In contrast, the DNA structure is an A–B hybrid state in the ethanol/water mixed solution. A fraying of terminal base-pairs is observed for the terminal cytosine. The ethylene glycol molecules preferentially form a ring structure around the phosphate groups to influence DNA conformation by hydrogen interactions, while water molecules tend to reside in the grooves. The repulsion between the negatively charged phosphate groups is screened by ethylene glycol molecules, preventing the repulsion from unwinding and extending the helix and thus making the conformation of DNA more compact.
基金The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayis University, Turkey, for the use of the Stoe IPDSII diffractometer (purchased under grant No F279 of the University Research Fund)
文摘The title compound,（E）-5-methoxy-2-（（4-methoxyphenylimino）methyl）phenol（C15H15NO3）,crystallizes in monoclinic,space group P21/c with a=9.4361（6）,b=10.6212（5）,c=12.9338（9）,β=93.064（5）o,V=1294.41（14）3,Z=4,Dc=1.320 g/cm3,F（000）=544,Rint=0.116,T=296 K,μ=0.09 mm-1,the final R=0.051 and wR=0.148 for 1836 observed reflections with I2σ（I）.An extensive two-dimensional network of C–H…O hydrogen bonds and π-ring interactions are responsible for the crystal stabilization.Intermolecular hydrogen bonds and C–H…π interactions produce R22（14）,R44（30） and R44（31） rings.In addition to the molecular geometry from X-ray experiment,the molecular geometry of the title compound in the ground state has been calculated using the semi-empirical（AM1 and PM3） and density functional theory method（DFT）（B3LYP） with 6-31G（d） basis set.To determine the conformational flexibility,molecular energy profile of the title compound was obtained by semi-empirical（PM3 and AM1） and DFT/B3LYP calculations with respect to the selected degree of torsional freedom,which varied from –180° to ＋180° in a step of 10°.
文摘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).
文摘Bacitracin consists of a mixture of several closely related polypeptide antibiotics produced from Bacillus licheniformis.The major component, Bacitracin A, is a cyclic dodecapeptide（Fig, 1）, which has strong bacteriocidal effect on the G+ bacteria. The bacteriocidal activity requires the presence of divalent cations such as Zn;, As we know, the biological function of ploypeptides and proteins are closely related to their three-dimensional structure. Bacitracin A is very important for the demonstration of the coordination site of metal and the relationship between
文摘Troponin is a thin filament-associated regulator of vertebrate striated muscle contraction. Troponin changes its structure upon Ca2+ binding to troponin C, one of the subunits of troponin, allowing myosin to interact with actin. We recently elucidated the molecular characteristics of the Japanese pearl oyster Pinctada fucata troponin C (Pifuc-TnC), revealing the possibilities that Pifuc-TnC and vertebrate muscle TnC play dissimilar roles in muscle contraction. Pifuc-TnC has four EF-hand motifs, but, unlike vertebrate TnC, only one (site IV) was predicted to bind Ca2+. To confirm the number of Ca2+-binding sites in Pifuc-TnC and whether Ca2+ binding induces a conformational change, we purified the full-length protein and a variant, Pifuc-TnC-E142Q (that has a mutation in the predicted Ca2+-binding site of site IV), following their expression in laboratory E. coli. Isothermal titration calorimetry demonstrated Ca2+ binding to Pifuc-TnC, whereas Pifuc-TnC-E142Q was unable to bind Ca2+, confirming that site IV is the only Ca2+-binding site in Pifuc-TnC. Pifuc-TnC eluted in a later fraction from a gel filtration column in the presence of Ca2+ compared with the condition when Ca2+ was absent. In contrast, the elution profiles of Pifuc-TnC-E142Q were equivalent in both the presence and absence of Ca2+, suggesting that Ca2+ binding to Pifuc-TnC induces a conformational change that delays its elution from the column. UV-absorption spectral analysis revealed that binding of Ca2+ to Pifuc-TnC caused an increase in absorption at a wavelength of approximately 250 nm, possibly because phenylalanine residues had been exposed on the surface of the molecule as a result of a conformational change. Differential scanning calorimetric analyses of Pifuc-TnC showed aggregation in the presence of Ca2+ in accordance with an increase of temperature, but no aggregation was seen in the absence of Ca2+. In combination, these findings suggest that Ca2+ binding to site IV induces a conformational change in Pifuc-TnC.
文摘A series of trans-4, 5-disubstituted -γ-butyrolactones are found to assume two different envelope conformations by means of nuclear magnetic resonance spectroscopy.
基金supported by US National Institutes of Health grant R01 AI44902 (to C Z )a Pre-doctoral Fellowship from the American Heart Association (to W C )
文摘Introduction Integrins are a large family of adhesion molecules broadly expressed on the surface of a wide variety of cells as heterodimers. Binding of integrins to ligands provides not only mechanical anchorage for the cell to another cell or
