26 research outputs found

    Discovery of Novel MDR-Mycobacterium tuberculosis Inhibitor by New FRIGATE Computational Screen

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    With 1.6 million casualties annually and 2 billion people being infected, tuberculosis is still one of the most pressing healthcare challenges. Here we report on the new computational docking algorithm FRIGATE which unites continuous local optimization techniques (conjugate gradient method) with an inherently discrete computational approach in forcefield computation, resulting in equal or better scoring accuracies than several benchmark docking programs. By utilizing FRIGATE for a virtual screen of the ZINC library against the Mycobacterium tuberculosis (Mtb) enzyme antigen 85C, we identified novel small molecule inhibitors of multiple drug-resistant Mtb, which bind in vitro to the catalytic site of antigen 85C

    Laboratory spectral reflectance studies aimed at providing clues to composition of refractory phases of comet 67P/CG's nucleus

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    We present 0.3-5 micron reflectance spectra of well-characterized powdered crystalline materials (Fe-sulfides, Mg-silicates), natural complex hydrocarbons and their mixtures that can serve as spectral analogues of comet 67P/CG's refractory phases. We study the ability of Fe-sulfides to suppress absorption bands of other cometary refractory components and to affect spectral slopes and reflectance values of the 67P/CG surface at different wavelengths from the near-UV to the IR. We investigate the evolution of organic absorption bands as a function of sulfide content in the mixtures and the possibility for detection of individual C-H stretching bands in reflectance spectra of 67P/CG

    Reflectance spectroscopy of natural organic solids, iron sulfides and their mixtures as refractory analogues for Rosetta/VIRTIS' surface composition analysis of 67P/CG

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    Analysis of 0.25-5 µm reflectance spectra provided by the Visible and InfraRed Thermal Imaging Spectrometer (VIRTIS) onboard Rosetta orbiter revealed that the surface of 67P/CG is dark from the near-UV to the IR and is enriched in refractory phases such as organic and opaque components. The broadness and complexity of the ubiquitous absorption feature around 3.2 µm suggest a variety of cometary organic constituents. For example, complex hydrocarbons (aliphatic and polycyclic aromatic) can contribute to the feature between 3.3 and 3.5 µm and to the low reflectance of the surface in the visible. Here we present the 0.25-5 µm reflectance spectra of well-characterized terrestrial hydrocarbon materials (solid oil bitumens, coals) and discuss their relevance as spectral analogues for a hydrocarbon part of 67P/CG's complex organics. However, the expected low degree of thermal processing of cometary hydrocarbons (high (H+O+N+S)/C ratios and low carbon aromaticities) suggests high IR reflectance, intense 3.3-3.5 µm absorption bands and steep red IR slopes that are not observed in the VIRTIS spectra. Fine-grained opaque refractory phases (e.g., iron sulfides, Fe-Ni alloys) intimately mixed with other surface components are likely responsible for the low IR reflectance and low intensities of absorption bands in the VIRTIS spectra of the 67P/CG surface. In particular, iron sulfides are common constituents of cometary dust, "cometary" chondritic IDPs, and efficient darkening agents in primitive carbonaceous chondrites. Their effect on reflectance spectra of an intimate mixture is strongly affected by grain size. We report and discuss the 0.25-5 µm reflectance spectra of iron sulfides (meteoritic troilite and several terrestrial pyrrhotites) ground and sieved to various particle sizes. In addition, we present reflectance spectra of several intimate mixtures of powdered iron sulfides and solid oil bitumens. Based on the reported laboratory data, we discuss the ability of iron sulfides to suppress absorption bands of other cometary refractory components and to affect the spectral slopes and reflectance values of the 67P/CG surface at different wavelengths from the near-UV to the IR

    Spectral reflectance properties of refractory components of comet 67P/CG's nucleus - insights from laboratory studies

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    Analysis of 0.25-5 μm reflectance spectra acquired by the Visible and InfraRed Thermal Imaging Spectrometer (VIRTIS) onboard Rosetta orbiter revealed that the surface of comet 67P/CG is dark from the near-UV to the IR and is enriched in refractory phases such as organic and opaque components. The broadness and complexity of the ubiquitous absorption feature around 3.2 μm suggest a variety of cometary organic constituents. For example, complex hydrocarbons can contribute to the feature between 3.2 and 3.5 μm and to the low reflectance of the surface in the visible. Relevance of natural macromolecular solids, such as solid oil bitumens (asphaltites, kerites, anthraxolites) and coals as spectral analogs for the hydrocarbon part of cometary refractory organics were discussed in detail in the literature. Fine-grained opaque refractory phases (e.g. iron sulfides, Fe-Ni alloys) are likely responsible for the low IR reflectance and low contrast of the 3.2 μm absorption band. Other non-icy constituents that may contribute to spectral reflectance properties of the 67P surface include amorphous and crystalline silicates. Here we report and discuss the 0.3-5 μm reflectance spectra of relevant Fe-sulfides (meteoritic troilite and several terrestrial pyrrhotites) ground and sieved to various particle sizes. We report the results of the synthesis, analyses, and/or spectral reflectance measurements of Fe-free low-Ca pyroxenes (ortho- and clinoenstatites), forsterites, and a high-Ca pyroxene (diopside). We present reflectance spectra of intimate mixtures of powdered Fe-sulfides with kerite (as an example of a relevant macromolecular organic solid) and synthetic orthoenstatite. We investigate and discuss the ability of Fe-sulfides to suppress absorption bands of other cometary refractory components and to affect the spectral slopes and reflectance values of the 67P/CG surface at different wavelengths from the near-UV to the IR. Finally, we discuss the evolution of organic absorption bands as a function of sulfide content in the mixtures and the possibility for detection of individual C-H stretching bands in the VIRTIS spectra of 67P/CG. We show that spectral reflectance of the ubiquitous dark material on the surface of 67P is mostly controlled by fine-grained opaques and organic refractories, while silicate components play a less significant role and are unlikely to contribute significantly to the VIRTIS spectra and to the observed spectral variations across the 67P surface. We demonstrate that fine-grained Fe-sulfides (troilite and pyrrhotite) are effective darkening agents from the near UV to IR that can explain the very low IR reflectance of the 67P nucleus. The shape of the VIRTIS spectra in the visible range is consistent with the presence of polyaromatic-rich organics together with Fe-sulfides. Fe-sulfides intimately mixed with other components significantly influence shapes and relative contrasts of absorption bands of other phases. If real, the fine structure in the VIRTIS spectra between 3.2 and 3.5 μm could be indicative of individual C-H absorption bands in aromatic structures, methyl and methylene groups. Further work is needed to clarify which species contribute to the broad complex 3.2-μm band in the VIRTIS spectra and to the spectral shape between 1.5 and 2.5 μm

    Temperature dependence of the heat diffusivity of proteins

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    In a combined experimental–theoretical study, we investigated the transport of vibrational energy from the surrounding solvent into the interior of a heme protein, the sperm whale myoglobin double mutant L29W-S108L, and its dependence on temperature from 20 to 70 K. The hindered libration of a CO molecule that is not covalently bound to any part of the protein but is trapped in one of its binding pockets (the Xe4 pocket) was used as the local thermometer. Energy was deposited into the solvent by IR excitation. Experimentally, the energy transfer rate increased from (30 ps)−1 at 20 K to (8 ps)−1 at 70 K. This temperature trend is opposite to what is expected, assuming that the mechanism of heat transport is similar to that in glasses. In order to elucidate the mechanism and its temperature dependence, nonequilibrium molecular dynamics (MD) simulations were performed, which, however, predicted an essentially temperature-independent rate of vibrational energy flow. We tentatively conclude that the MD potentials overestimate the coupling between the protein and the CO molecule, which appears to be the rate-limiting step in the real system at low temperatures. Assuming that this coupling is anharmonic in nature, the observed temperature trend can readily be explained

    Width of the phi meson in nuclear matter

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    The ratios of the cross sections for I -meson production induced by 2.83-GeV protons on Cu, Ag, and Au nuclei to the respective cross section for C nuclei were measured at the ANKE-COSY facility in the momentum range of 0.6-1.6 GeV/c and the angular range of 0 -8 . The product I mesons were identified by their decay I -> K (+) K (-'). The procedure used to separate kaon pairs was described in detail, and all sources of the background and their contribution to the resulting error in the values found for the above cross-section ratios were analyzed. The A dependence of the cross section for I -meson production was shown to obey the A (0.56+-0.03) law. The total width of the I meson at a normal nuclear density was extracted from a comparison of the measured cross-section ratios with the results of calculations based on two theoretical models. The resulting width value exceeds substantially both the vacuum width and the width expected in the absence of the nuclear-matter effect on the properties of the I meson

    The organic-rich surface of comet 67P/Churyumov-Gerasimenko as seen by VIRTIS/Rosetta

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    The VIRTIS (Visible, Infrared and Thermal Imaging Spectrometer) instrument on board the Rosetta spacecraft has provided evidence of carbon-bearing compounds on the nucleus of the comet 67P/Churyumov-Gerasimenko. The very low reflectance of the nucleus (normal albedo of 0.060 −/+ 0.003 at 0.55 micrometers), the spectral slopes in visible and infrared ranges (5 to 25 and 1.5 to 5% k/Å), and the broad absorption feature in the 2.9-to-3.6 micrometer range present across the entire illuminated surface are compatible with opaque minerals associated with nonvolatile organic macromolecular materials: a complex mixture of various types of carbon-hydrogen and/or oxygen-hydrogen chemical groups, with little contribution of nitrogen-hydrogen groups. In active areas, the changes in spectral slope and absorption feature width may suggest small amounts of water-ice. However, no ice-rich patches are observed, indicating a generally dehydrated nature for the surface currently illuminated by the Sun
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