Evaluation of docking/scoring approaches: A comparative study based on MMP3 inhibitors

An increasing number of docking/scoring programs are available that use different sampling and scoring algorithms. A reliable scoring function is the crucial element of such approaches. Comparative studies are needed to evaluate their current capabilities. DOCK4 with force field and PMF scoring as well as FlexX were used to evaluate the predictive power of these docking/scoring approaches to identify the correct binding mode of 61 MMP-3 inhibitors in a crystal structure of stromelysin and also to rank them according to their different binding affinities. It was found that DOCK4/PMF scoring performs significantly better than FlexX and DOCK4/FF in both ranking ligands and predicting their binding modes. Most notably, DOCK4/PMF was the only scoring/docking approach that found a significant correlation between binding affinity and predicted score of the docked inhibitors. However, comparing only those cases where the correct binding mode was identified (scoring highest among sampled poses), FlexX showed the best `fine tuning' (lowest rmsd) in predicted binding modes. The results suggest that not so much the sampling procedure but rather the scoring function is the crucial element of a docking program.     

Curing temperature- and concentration-dependent dielectric properties of cross-linked poly-4-vinylphenol (PVP)

In this paper, dielectric properties of various thick PVP films cured at temperatures between 125° C and 200 °C are investigated. The thicknesses of PVP films are adjusted by varying their concentration in PGMEA solvent from 10 wt% to 2.5 wt%. Through FT-IR, C–V, SEM, and AFM analyses, the optimum curing process temperatures (150 °C for 10 wt% and 7.5 wt% samples, and 175 °C for 5 wt% samples) where PET substrates can be thermally endured are proposed in terms of their low hysteresis voltage in the C–V curve (1–2 V in 10 wt% samples, below 1 V in 7.5 wt% samples, and 0.5 V in 5 wt% samples).     

Development and assessment of scoring functions for protein identification using PMF data

PMF is one of the major methods for protein identification using the MS technology. It is faster and cheaper than MS/MS. Although PMF does not differentiate trypsin-digested peptides of identical mass, which makes it less informative than MS/MS, current computational methods for PMF have the potential to improve its detection accuracy by better use of the information content in PMF spectra. We developed a number of new probability-based scoring functions for PMF protein identification based on the MOWSE algorithm. We considered a detailed distribution of matching masses in a protein database and peak intensity, as well as the likelihood of peptide matches to be close to each other in a protein sequence. Our computational methods are assessed and compared with other methods using PMF data of 52 gel spots of known protein standards. The comparison shows that our new scoring schemes have higher or comparable accuracies for protein identification in comparison to the existing methods. Our software is freely available upon request. The scoring functions can be easily incorporated into other proteomics software packages.     

PM2.5 in an industrial district of Zhengzhou,China:Chemical composition and source apportionment

Zhengzhou is a developing city in China,that is heavily polluted by high levels of particulate matter.In this study.fine particulate matter(PM_2.5) was collected and analyzed for their chemical composition（soluble ions,elements,elemental carbon（EC） and organic carbon（OC）） in an industrial district of Zhengzhou in 2010.The average concentrations of PM_2.5 were 181,122,186 and 211μg/m³ for spring,summer, autumn and winter,respectively,with an annual average of 175μg/m³,far exceeding the PM_2.5 regulation of USA National Air Quality Standards（15μg/m³）.The dominant components of PM_2.5 in Zhengzhou were secondary ions（sulphate and nitrate） and carbon fractions.Soluble ions,total carbon and elements contributed 41%,13%and 3%of PM_2.5 mass,respectively.Soil dust,secondary aerosol and coal combustion, each contributing about 26%,24%and 23%of total PM_2.5 mass,were the major sources of PM_2.5,according to the result of positive matrix factorization analysis.A mixed source of biomass burning,oil combustion and incineration contributed 13%of PM_2.5.Fine particulate matter arising from vehicles and industry contributed about 10%and 4%of PM_2.5,respectively.     

Source Apportionment Research of Fine Particulate Matter in the Atmosphere by PAHs

Haze weather frequently occurs in many cities in China. Polycyclic aromatic hydrocarbons(PAHs) in fine particulate matter(PM_2.5) can adversely affect the environment and human health. In this paper, PM_2.5 samples were collected at nine sites in a city in northeastern China from September 2013 to October 2014. Sixteen USEPA(US Evironment Protection Agency) priority PAHs in PM_2.5 were analyzed to determine their spatial and temporal distribution characteristics. The source apportionment of PAHs was conducted with the Positive Matrix Factorization(PMF) model. The results indicate that the concentrations of total PAHs(T-PAHs) in PM_2.5 are within the range of 0.26 to 72.48 ng/m³. The seasonal variation of T-PAHs is winter >spring >autumn >summer, and the space distribution of PAHs is JZP >DP >BFH >LP >EESA >IPT >CP >HZMC >JYP. In all types of PAHs, three-ring and five-ring PAHs are significantly prominent(62%) in the heating period due to petrogenic sources and traffic emissions. Middle- and high-ring PAHs in the non-heating period are caused by coal combustion and vehicle exhaust, which accounts for 77% of the total emissions. The source apportionment results obtained by the diagnostic ratio of PAHs reflect that coal burning, traffic and other sources have a distinct influence on PAH emissions in this city. Six factors are defined by PMF v5.0, namely, coke oven emissions(7.7%), biomass burning(44.3%), petrogenic sources(10.7%), coal combustion(10.4%), gasoline engine emissions(16.7%), and diesel engine emissions(10.3%). The results indicate that the PAHs in PM_2.5 in the city are primarily caused by combustion processes and vehicle exhaust.     

A virtual high throughput screen for high affinity cytochrome P450cam substrates. Implications for in silico prediction of drug metabolism

Structure-based virtual screening techniques require reliable scoring functions to discriminate potential substrates effectively. In this study we compared the performance of GOLD, PMF, DOCK and FlexX scoring functions in FlexX flexible docking to cytochrome P450cam binding site. Crystal structures of protein-substrate complexes were most effectively reproduced by the FlexX/PMF method. On the other hand, the FlexX/GOLD approach provided the best correlation between experimental binding constants and predicted scores. Binding modes selected by the FlexX/PMF approach were rescored by GOLD to obtain a reliable measure of binding energetics. The effectiveness of the FlexX/PMF/GOLD method was demonstrated by the correct classification of 32 out of the 33 experimentally studied compounds and also in a virtual HTS test on a library of 10,000 compounds. Although almost all the available functions were developed to be general, our study on cytochrome P450cam substrates suggests that careful selection or even tailoring the scoring function might increase the prediction power of virtual screens significantly. The FlexX/PMF/GOLD methodology was tested on cytochrome P450 3A4 substrates and inhibitors. This preliminary study revealed that the combined function was able to recognise 334 out of the 345 compounds bound to 3A4.     

高双折射Sagnac环透射特性的理论与实验研究

 采用传输矩阵分析法、数值模拟和实验研究相结合的方法研究了由光耦合器（OC）、偏振控制器（PC）和保偏光纤（PMF）组成的高双折射Sagnac干涉环的透射特性。理论分析了PMF特性和PC状态对输出特性的影响,并通过数值模拟得到了PMF长度、双折射率（Δn）和PC状态不同时所对应的透射光谱。最后通过实验验证得出了波长间隔只由PMF的长度和双折射率Δn决定,透射率大小只由PC状态决定,而透射谱的峰值位置由PMF和PC状态共同决定的规律。实验结果与理论分析结果非常一致,对Sagnac环透射规律的研究对这种可调谐滤波器在多波长光纤激光器中的应用具有一定的参考价值。     

A Novel Protein Found in Selenium-rich Silkworm Pupas

Selenium(Se)is well known for its cancer-preventive function1.In our previous work,silkworm pupas from Ziyang county of Shanxi Province,one of the two largest Se-rich areas in China,was found to have Se content215times higher than that from Luoyang which is a normal region in China2.Meanwhile,Se-rich amino acids extracted from Ziyang pupas could efficiently induce the apoptosis of human hepatoma cells SMMC-7721.In order to find out the effective component responsible for this carcinostat…     

Potentials of mean force for hydrophobic interactions between hydrocarbons in water solution: dependence on temperature,solute shape,and solute size

We carried out molecular dynamics (MD) simulations with the AMBER force field for four pairs of spherical dimers of different size (neopentane, bicyclooctane, adamantane, and fullerene‐C₆₀) using the TIP3P model of water as solvent. For comparison, we performed MD simulations for a linear molecule of n‐pentane at the same conditions. To assess the entropy contribution to the Gibbs free energy, MD simulations were run at three different temperatures of 273 K, 323 K, and 348 K, respectively, using umbrella‐sampling/the WHAM method. The stability of dimers is described by a potential of mean force (PMF). The shape of PMF curves for hydrophobic interactions is characteristic, and entails a contact minimum, a solvent‐separated minimum, and a desolvation maximum. The depth and position of the contact minimum for each pair change with the size of the nonpolar particle, and are consequently shifted to a larger distance for larger molecules. Additionally, the Lennard–Jones contribution to the PMF increases simultaneously with an increase in particle size. For a linear dimer, the contact minimum is shifted to a shorter distance than it is for spherical systems with the same number of carbon atoms. The contact minima on PMF curves increase with temperature, suggesting that the association entropy is positive. Dimensionless PMF curves showed a low dependency (near contact minima regions) on temperature, as the association entropy is low. Copyright © 2014 John Wiley & Sons, Ltd.     

Designing PMF with negative tap coefficient

DIRECT global optimization algorithm is innovatively used in design of PMF. Tap coefficient is attained by achieving DIRECT algorithm with C language and Matlab language is employed to simulate the amplitude response of filters. We have designed PMF (photonic microwave filter) with negative tap coefficient and then optimize the design. The minimum shape factor is as low as 1.3180. The results show that the algorithm is highly efficient in designing filter and can produce necessary passband and stopband response characteristics. In the meantime, transition band becomes steeper in the process of further optimization and the shape factor is closer to 1.