Insight into the Dynamic Interaction of Different Carbohydrates with Human Surfactant Protein D: Molecular Dynamics Simulations

The unbinding process of three monosaccharides―galactose, glucose, and mannose―from human surfactant protein D (hSP-D) was investigated by the molecular docking and molecular dynamics methods to explore the cause of different dynamic interaction between these monosaccharides and the protein. The results show that the low affinity of galactose for hSP-D is attributed to the different binding conformation from the other two monosaccharides. The sugar coordinates to the calcium ion by the hydroxyl groups in the C2 and C3 atoms, so it cannot form the effective interaction with hSP-D. Glucose and mannose have similar binding conformations with hSP-D. Their difference in the affinity is induced by the interaction between the hydroxyl group in the C2 atom and the residue Asp325. The direction of the hydroxyl group in mannose results in the formation of the hydrogen bond with Asp325 and further makes mannose hydrogen-bond to the residues Glu329 and Arg343 by the hydroxyl groups in the C3, C4, and C6 atoms. As glucose only forms three hydrogen bonds with the residues Glu321, Asn323, and Glu329 by the hydroxyl groups in the C3 and C4 atoms, its interaction with hSP-D is weaker than that of mannose. Thus glucose has a lower energy barrier of dissociation. This work could provide the more penetrating understanding of hSP-D physiological functions

Molecular Insights into the Heterotropic Allosteric Mechanism in Cytochrome P450 3A4-Mediated Midazolam Metabolism

Cytochrome P450 3A4 (CYP3A4) is the main P450 enzyme for drug metabolism and drug–drug interactions (DDIs), as it is involved in the metabolic process of approximately 50% of drugs. A detailed mechanistic elucidation of DDIs mediated by CYP3A4 is commonly believed to be critical for drug optimization and rational use. Here, two typical probes, midazolam (MDZ, substrate) and testosterone (TST, allosteric effector), are used to investigate the molecular mechanism of CYP3A4-mediated heterotropic allosteric interactions, through conventional molecular dynamics (cMD) and well-tempered metadynamics (WT-MTD) simulations. Distance monitoring shows that TST can stably bind in two potential peripheral sites (Site 1 and Site 2) of CYP3A4. The binding of TST at these two sites can induce conformational changes in CYP3A4 flexible loops on the basis of conformational analysis, thereby promoting the transition of the MDZ binding mode and affecting the ratio of MDZ metabolites. According to the results of the residue interaction network, multiple allosteric communication pathways are identified that can provide vivid and applicable insights into the heterotropic allostery of TST on MDZ metabolism. Comparing the regulatory effects and the communication pathways, the allosteric effect caused by TST binding in Site 2 seems to be more pronounced than in Site 1. Our findings could provide a deeper understanding of CYP3A4-mediated heterotropic allostery at the atomic level and would be helpful for rational drug use as well as the design of new allosteric modulators

Additional file 1 of Association between body mass index and myopia in the United States population in the National Health and Nutrition Examination Surveys 1999 to 2008: a cross-sectional study

Additional file 1: Table S1. Frequency and proportion of missing values for all variables

Molecular Basis of the Recognition of Cholesterol by Cytochrome P450 46A1 along the Major Access Tunnel

CYP46A1 is an important potential target for the treatment of Alzheimer’s disease (AD), which is the most common neurodegenerative disease among older individuals. However, the binding mechanism between CYP46A1 and substrate cholesterol (CH) has not been clarified and will not be conducive to the research of relevant drug molecules. In this study, we integrated molecular docking, molecular dynamics (MD) simulations, and adaptive steered MD simulations to explore the recognition and binding mechanism of CYP46A1 with CH. Two key factors affecting the interaction between CH and CYP46A1 are determined: one is a hydrophobic cavity formed by seven hydrophobic residues (F80, Y109, L112, I222, W368, F371, and T475), which provides nonpolar interactions to stabilize CH, and the other is a hydrogen bond formed by H81 and CH, which ensures the binding direction of CH. In addition, the tunnel analysis results show that tunnel 2a is identified as the primary pathway of CH. The entry of CH induces tunnel 2e to close and tunnel w to open. Our results may provide effective clues for the design of drugs based on the substrate for AD and improve our understanding of the structure–function of CYP46A1

Additional file 1 of Effects of electroconvulsive therapy on functional brain networks in patients with schizophrenia

Additional file 1

Synthesis, liquid crystalline mesophases and morphologies of diblock copolymers composed of a poly(dimethylsiloxane) block and a nematic liquid crystalline block

<p>In this study, a series of liquid crystalline diblock copolymers, composed of a soft poly(dimethylsiloxane) (PDMS) block with a defined length and a side-on liquid crystalline poly(3ʹʹ-acryloyloxypropyl 2,5-di(4ʹ-butyloxybenzoyloxy) benzoate) (P3ADBB) block with different lengths, are synthesised by the atom transfer radical polymerisation. The macromolecular structures, liquid crystalline properties and the microphase-separated morphologies of the diblock copolymer are investigated by ¹H NMR, FT-IR, GPC, POM, DSC and TEM. The results show that the well-defined diblock copolymers (PDMS_n-<i>b</i>-P3ADBB_m) possess four different soft/rigid ratios (<i>n</i> = 58, <i>m</i> = 10, 25, 42, 66) and relatively narrow molecular distributions (PDI ≤ 1.30). P3ADBB blocks of the copolymers show nematic sub-phases, which are identical to the mesomorphic behaviour of the homopolymer P3ADBB. After being annealed at 90°C in a vacuum oven for 48 h, the copolymers form a lamellar morphology when <i>m</i> = 10 and morphologies of PDMS spheres embedded in P3ADBB matrix when <i>m</i> = 25, 42 and 66.</p

Removal of Thiophenic Sulfurs Using an Extractive Oxidative Desulfurization Process with Three New Phosphotungstate Catalysts

Three Keggin-type phosphotungstates, i.e. [C5H5NH]3PW12O40, [C4H6N2H]3PW12O40·3C4H6N2 and [(C4H9)4N]3PW12O40, were synthesized and characterized by elemental analysis, X-ray diffraction, and infrared spectra, meanwhile their catalysis in an extractive catalytic oxidative desulfurization process was studied with ionic liquid (IL) as extractant and H2O2 as oxidant. The main factors affecting the desulfurization process were investigated, including temperature, hydrophobicity of IL, and variety of S-compounds, as well as the amount of catalyst, IL, and H2O2. Under the optimal conditions, the S-content of DBT oil can be decreased from 1000 to 2 ppm. A new interpretation is proposed for the current process, in which IL is assumed as a reaction phase, and the amount of the extracted S-compound and the peroxidized catalyst wherein greatly affect the desulfurization rate. Besides, the IL with the dissolved catalyst can be reused many times and regenerated easily

Data for "Effect of elevated tropospheric ozone on soil carbon and nitrogen: A meta-analysis"

These data were extracted from 41 peer-reviewed studies to quantify the impact of O3 on ten variables associated with soil C and N, i.e., total C (TC, including soil organic C), total N (TN), dissolved organic C (DOC), ammonia N (NH4+), nitrate N (NO3-), microbial biomass C (MBC) and N (MBN), rates of nitrification (NTF) and denitrification (DNF), as well as C/N ratio. The data were acquired from 17 experiments performed at 25°28' N to 60°49' N latitude and 88°14' W to 123°24' E longitude. The mean annual temperature (MAT) ranged from 1.1 °C to 26.6 °C, and the mean annual precipitation (MAP) ranged from 460 mm to 1280 mm. The average increment in [O3] across all studies was 27.6±18.7 nL/L.<br

Surface Tension and Dilational Viscoelasticity of Water in the Presence of Surfactants Tyloxapol and Triton X-100 with Cetyl Trimethylammonium Bromide at 25 °C

Surface tension and dilational viscoelasticity of water in the presence of surfactants Tyloxapol and Triton X-100 with cetyl trimethylammonium Bromide (CTAB) at 25 °C are investigated. The results show that there is synergistic behavior in both the mixtures at higher mole fraction of nonionic surfactant. According to the Rubingh and Rosen theory, the results predict nonideal mixing and attractive interaction between the constituent surfactants in the mixed micelle and layer. By using the Maeda theory, the results suggest the chain−chain interaction among surfactants does not seem to be high. The surface dilational viscoelasticity results show that the Tyloxapol adsorption layer has the highest dilational modulus |ε| value among three single surfactants. Also, it indicates the |ε| maximum values of surfactant mixtures are usually between that of the single surfactant. Moreover, it is worth noting that the |ε| maximum values of Tyloxapol/CTAB mixtures are always higher than those of TX-100/CTAB ones

Excited-State Conjugation/De-Conjugation Driven Nonradiative Thermal Deactivation for Developing Fluorogenic Probes to Diagnose Cancers

Fluorogenic probes have shown great potential in imaging biological species as well as in diagnosing diseases, especially cancers. However, the fluorogenic mechanisms are largely limited to a few photophysical processes to date, typically including photoinduced electron transfer (PeT), fluorescence resonant energy transfer (FRET), and intramolecular charge transfer (ICT). Herein, by calculations and experiments, we set forth that the inhibition of the excited-state π-conjugation in meso-ester Si-rhodamine SiR-COOM or the de-π-conjugation in meso-ester cyanine 5 Cy5-COOM via the “ester-to-carboxylate” conversion can operate as a general fluorogenic mechanism to fabricate fluorogenic probes. Based on the mechanism and considering the higher chemical stability of Cy5-COOM than that of SiR-COOM, we developed, as a proof-of-concept, three fluorogenic probes Cy5-APN, Cy5-GGT, and Cy5-NTR on the basis of the Cy5-COOM platform for sensing cancer biomarkers aminopeptidase N (APN), γ-glutamyltranspeptidase (GGT), and nitroreductase (NTR), respectively, and demonstrated their outstanding performances in distinguishing between cancerous and normal tissues with the high tumor-to-normal tissue ratios in the range of 9–14