212 research outputs found
The role of the charge state of PAHs in ultraviolet extinction
Aims: We explore the relation between charge state of polycyclic aromatic
hydrocarbons (PAHs) and extinction curve morphology. Methods: We fit extinction
curves with a dust model including core-mantle spherical particles of mixed
chemical composition (silicate core, and carbonaceous layers),
and an additional molecular component. We use exact methods to calculate the
extinction due to classical particles and accurate computed absorption spectra
of PAHs in different charge states, for the contribution due to the molecular
component, along a sample of five rather different lines of sight. Results: A
combination of classical dust particles and mixtures of real PAHs
satisfactorily matches the observed interstellar extinction curves. Variations
of the spectral properties of PAHs in different charge states produce changes
consistent with the varying relative strengths of the bump and non-linear
far-UV rise.Comment: 5 pages, 3 figures, Astronomy & Astrophysics Letters, in pres
Time-Dependent Density Functional Theory Investigation on the Electronic and Optical Properties of Poly-C,Si,Ge-acenes
We report a comparative computational investigation on the first six members of linear poly-C,Si,Ge-acenes (X4n+2H2n+4, X = C,Si,Ge; n = 1, 2, 3, 4, 5, 6). We performed density functional theory (DFT) and time-dependent DFT calculations to compare morphological, electronic, and optical properties. While C-acenes are planar, Si-and Ge-acenes assume a buckled configuration. Electronic properties show similar trends as a function of size for all families. In particular, differently from C-based compounds, in the case of both Si-and Ge-acenes, the excitation energies of the strongest low-lying electronic transition (β peaks) span the visible region of the spectrum, demonstrating their size tunability. For all families, we assessed the plasmonic character of this transition and found a linear relationship for the wavelength-dependence of the β peaks as a function of the number of rings. A similar slope of about 56 nm is observed for Si-and Ge-acenes, although the peak positions of the former are located at lower wavelengths. Outcomes of this study are compared with existing theoretical results for 2D lattices and nanoribbons, and experiments where available
Molecular interactions of carbapenem antibiotics with the multidrug efflux transporter acrb of escherichia coli
The drug/proton antiporter AcrB, engine of the major efflux pump AcrAB(Z)-TolC of Escherichia coli and other bacteria, is characterized by its impressive ability to transport chemically diverse compounds, conferring a multi-drug resistance (MDR) phenotype. Although hundreds of small molecules are known to be AcrB substrates, only a few co-crystal structures are available to date. Computational methods have been therefore intensively employed to provide structural and dynamical fingerprints related to transport and inhibition of AcrB. In this work, we performed a systematic computational investigation to study the interaction between representative carbapenem antibiotics and AcrB. We focused on the interaction of carbapenems with the so-called distal pocket, a region known for its importance in binding inhibitors and substrates of AcrB. Our findings reveal how the different physico-chemical nature of these antibiotics is reflected on their binding preference for AcrB. The molecular-level information provided here could help design new antibiotics less susceptible to the efflux mechanism
Efficient calculation of van der Waals dispersion coefficients with time-dependent density functional theory in real time: application to polycyclic aromatic hydrocarbons
The van der Waals dispersion coefficients of a set of polycyclic aromatic
hydrocarbons, ranging in size from the single-cycle benzene to circumovalene
(C66H20), are calculated with a real-time propagation approach to
time-dependent density functional theory (TDDFT). In the non-retarded regime,
the Casimir-Polder integral is employed to obtain C6, once the dynamic
polarizabilities have been computed at imaginary frequencies with TDDFT. On the
other hand, the numerical coefficient that characterizes the fully retarded
regime is obtained from the static polarizabilities. This ab initio strategy
has favorable scaling with the size of the system - as demonstrated by the size
of the reported molecules - and can be easily extended to obtain higher order
van der Waals coefficients.Comment: submitted to J. Chem. Phy
Holo-like and Druggable Protein Conformations from Enhanced Sampling of Binding Pocket Volume and Shape
Understanding molecular recognition of small molecules by proteins in atomistic detail is key for drug design. Molecular docking is a widely used computational method to mimic ligand-protein association in silico. However, predicting conformational changes occurring in proteins upon ligand binding is still a major challenge. Ensemble docking approaches address this issue by considering a set of different conformations of the protein obtained either experimentally or from computer simulations, e.g., molecular dynamics. However, holo structures prone to host (the correct) ligands are generally poorly sampled by standard molecular dynamics simulations of the apo protein. In order to address this limitation, we introduce a computational approach based on metadynamics simulations called ensemble docking with enhanced sampling of pocket shape (EDES) that allows holo-like conformations of proteins to be generated by exploiting only their apo structures. This is achieved by defining a set of collective variables that effectively sample different shapes of the binding site, ultimately mimicking the steric effect due to the ligand. We assessed the method on three challenging proteins undergoing different extents of conformational changes upon ligand binding. In all cases our protocol generates a significant fraction of structures featuring a low RMSD from the experimental holo geometry. Moreover, ensemble docking calculations using those conformations yielded in all cases native-like poses among the top-ranked ones
Electronic and optical properties of families of polycyclic aromatic hydrocarbons: a systematic (time-dependent) density functional theory study
Homologous classes of Polycyclic Aromatic Hydrocarbons (PAHs) in their
crystalline state are among the most promising materials for organic
opto-electronics. Following previous works on oligoacenes we present a
systematic comparative study of the electronic, optical, and transport
properties of oligoacenes, phenacenes, circumacenes, and oligorylenes. Using
density functional theory (DFT) and time-dependent DFT we computed: (i)
electron affinities and first ionization energies; (ii) quasiparticle
correction to the highest occupied molecular orbital (HOMO)-lowest unoccupied
molecular orbital (LUMO) gap; (iii) molecular reorganization energies; (iv)
electronic absorption spectra of neutral and charged systems. The
excitonic effects are estimated by comparing the optical gap and the
quasiparticle corrected HOMO-LUMO energy gap. For each molecular property
computed, general trends as a function of molecular size and charge state are
discussed. Overall, we find that circumacenes have the best transport
properties, displaying a steeper decrease of the molecular reorganization
energy at increasing sizes, while oligorylenes are much more efficient in
absorbing low-energy photons in comparison to the other classes.Comment: 26 pages, 9 figures, 4 tables, accepted for pubblication in Chemical
Physics (14/04/2011
Optical spectrum of proflavine and its ions
Motivated by possible astrophysical and biological applications we calculate
visible and near UV spectral lines of proflavine (C13H11N3,
3,6-diaminoacridine) in vacuum, as well as its anion, cation, and dication. The
pseudopotential density functional and time-dependent density functional
methods are used. We find a good agreement in spectral line positions
calculated by two real-time propagation methods and the Lanczos chain method.
Spectra of proflavine and its ions show characteristic UV lines which are good
candidates for a detection of these molecules in interstellar space and various
biological processes
A framework for dissecting affinities of multidrug efflux transporter AcrB to fluoroquinolones
Sufficient concentration of antibiotics close to their target is key for antimicrobial action. Among the tools exploited by bacteria to reduce the internal concentration of antibiotics, multidrug efflux pumps stand out for their ability to capture and expel many unrelated compounds out of the cell. Determining the specificities and efflux efficiency of these pumps towards their substrates would provide quantitative insights into the development of antibacterial strategies. In this light, we developed a competition efflux assay on whole cells, that allows measuring the efficacy of extrusion of clinically used quinolones in populations and individual bacteria. Experiments reveal the efficient competitive action of some quinolones that restore an active concentration of other fluoroquinolones. Computational methods show how quinolones interact with the multidrug efflux transporter AcrB. Combining experiments and computations unveils a key molecular mechanism acting in vivo to detoxify bacterial cells. The developed assay can be generalized to the study of other efflux pumps
Electronic absorption spectra of hydrogenated protonated naphthalene and proflavine
We study hydrogenated cations of two polycyclic hydrocarbon molecules as
models of hydrogenated organic species that form in the interstellar medium.
Optical spectra of the hydrogenated naphthalene cation Hn-C10H8^+ for n=1,2,
and 10, as well as of the astrobiologically interesting hydrogenated proflavine
cation Hn-C13H11N3^+ for n=1 and 14, are calculated. The pseudopotential time
dependent density functional theory is used. It is found that the fully
hydrogenated proflavine cation H14-C13H11N3^+ shows a broad spectrum where
positions of individual lines are almost lost. The positions of lines, their
shapes, and intensities change in hydronaphthalene and hydroproflavine cations
showing that hydrogen additions induce substantially different optical spectra
in a comparison to base polycyclic hydrocarbon cations. One calculated line in
the visible spectrum of H10-C10H8^+, and one in the visible spectrum of
H-C13H11N3^+ are close to the measured diffuse interstellar bands. We also
present positions of near-UV lines.Comment: 6 pages, 3 figures, 3 tables, Accepted in MNRA
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