A5059598818- Antibiotic Resistance in Bacteria
- Surface and Thin Film Phenomena
- Drug Transport and Resistance Mechanisms
- Bacterial Genetics and Biotechnology
- Advanced Chemical Physics Studies
- Chemistry and Stereochemistry Studies
- Antibiotics Pharmacokinetics and Efficacy
- Protein Structure and Dynamics
- Cancer therapeutics and mechanisms
- nanoparticles nucleation surface interactions
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Hemoglobin structure and function
- Quantum, superfluid, helium dynamics
- Semiconductor Quantum Structures and Devices
- Chemical and Physical Properties of Materials
- Bacteriophages and microbial interactions
- Physics of Superconductivity and Magnetism
- Nanopore and Nanochannel Transport Studies
- Spectroscopy and Quantum Chemical Studies
- Metal complexes synthesis and properties
- Semiconductor materials and devices
- Analytical Chemistry and Chromatography
- Lipid Membrane Structure and Behavior
- Electron and X-Ray Spectroscopy Techniques
University of Cagliari
2016-2025
Istituto Nazionale di Fisica Nucleare, Sezione di Cagliari
2007-2021
Istituto Officina dei Materiali
2010-2019
Scuola Internazionale Superiore di Studi Avanzati
2005-2009
Italian Institute of Technology
2008-2009
Max Planck Institute for Dynamics and Self-Organization
2009
Constructor University
2008
Universidade do Porto
2008
AREA Science Park
2007
Leiden University
2005
A number of diverse bulk properties the zincblende and wurtzite III-V nitrides AlN, GaN, InN, are predicted from first principles within density functional theory using plane-wave ultrasoft pseudopotential method, both LDA (local density) GGA (generalized gradient) approximations to exchange-correlation functional. Besides structure cohesion, we study formation enthalpies (a key ingredient in predicting defect solubilities surface stability), spontaneous polarizations piezoelectric constants...
Significance AcrB is one of the major multidrug resistance-conferring antibiotic efflux pumps from pathogenic bacteria. We have designed and produced periplasmic, substrate binding domain solved its crystal structure in complex with multiple novel pyranopyridine inhibitors, as well drugs transported by AcrB. The structural data are corroborated various cellular assays molecular dynamics (MD) simulations, allow us to propose a mechanism for inhibition. Furthermore, results provide platform...
Knowledge of the structures formed by proteins and small molecules is key to understand molecular principles chemotherapy for designing new more effective drugs. During early stage a drug discovery program, it customary predict ligand-protein complexes in silico, particularly when screening large compound databases. While virtual based on docking widely used this purpose, generally fails mimicking binding events associated with conformational changes protein, latter involve multiple domains....
The incidence of multidrug-resistant bacterial infections is increasing globally and the need to understand underlying mechanisms paramount discover new therapeutics. efflux pumps Gram-negative bacteria have a broad substrate range transport antibiotics out bacterium, conferring intrinsic multidrug resistance (MDR). genomes pre- posttherapy MDR clinical isolates Salmonella Typhimurium from patient that failed antibacterial therapy died were sequenced. In isolate we identified novel G288D...
Efflux pumps of the resistance nodulation division (RND) superfamily, such as AcrB, make a major contribution to multidrug in Gram-negative bacteria. The development inhibitors RND would improve efficacy current and next-generation antibiotics. To date, however, only one inhibitor has been cocrystallized with AcrB. Thus, silico structure-based analysis is essential for elucidating interaction between other efflux pumps. In this work, we used computer docking molecular dynamics simulations...
Employing first principles total energy calculations we have studied the behavior of Ga and Al adatoms on GaAs(001)- $\ensuremath{\beta}2$ surface. Beside adsorption site identify two diffusion channels that are characterized by different adatom-surface dimer interaction. Both affect adatom migration: in one channel jumps across surface dimers leaves bonds intact; other broken. The taken into account to derive effective barriers. We find a strong anisotropy for both and, agreement with...
The tripartite complex AcrAB-TolC is the major efflux system in Escherichia coli. It extrudes a wide spectrum of noxious compounds out bacterium, including many antibiotics. Its active part, homotrimeric transporter AcrB, responsible for selective binding substrates and energy transduction. Based on available crystal structures biochemical data, transport by AcrB has been proposed to take place via functional rotation, which each monomer assumes particular conformation. However, there no...
The tripartite efflux pump AcrAB-TolC is responsible for the intrinsic and acquired multidrug resistance in Escherichia coli. Its active part, homotrimeric transporter AcrB, charge of selective binding substrates energy transduction. mutation F610A has been shown to significantly reduce minimum inhibitory concentration doxorubicin many other substrates, although F610 does not appear interact strongly with them. Biochemical study transport kinetics AcrB yet possible, except some β-lactams,...
Efflux is an important mechanism in Gram-negative bacteria conferring multidrug resistance. Inhibition of efflux encouraging strategy to restore the antibacterial activity antibiotics. Chlorpromazine and amitriptyline have been shown behave as inhibitors. However, their mode action poorly understood. Exposure Salmonella enterica serovar Typhimurium Escherichia coli chlorpromazine selected for mutations within genes encoding RamR MarR, regulators tripartite pump AcrAB-TolC. Further...
Resistance-Nodulation-cell Division (RND) transporters AcrB and AcrD of Escherichia coli expel a wide range substrates out the cell in conjunction with AcrA TolC, contributing to onset bacterial multidrug resistance. Despite sharing an overall sequence identity ~66% (similarity ~80%), these RND feature distinct substrate specificity patterns whose underlying basis remains elusive. We performed exhaustive comparative analyses putative binding pockets considering crystal structures, homology...
Abstract With the spreading of antibiotic resistance, translocation antibiotics through bacterial envelopes is crucial for their antibacterial activity. In Gram-negative bacteria, interplay between membrane permeability and drug efflux pumps must be investigated as a whole. Here, we quantified intracellular accumulation series fluoroquinolones in population individual cells Escherichia coli according to expression AcrB transporter. Computational results supported levels measured...
Copper−1,10-phenanthroline (phen) complexes Cu(phen)2, Cu(2-Clip-phen), and Cu(3-Clip-phen) (Clip = a serinol bridge between the phen parts) are typically employed as DNA-cleaving agents now becoming increasingly important for building multifunctional drugs with improved cytotoxic properties. For instance, has been combined distamycin-like minor-groove binders cisplatin-derivatives, leading to promising results. Density Functional Theory (DFT) docking calculations well molecular dynamics...
We present an on-line database of all-atom force-field parameters and molecular properties compounds with antimicrobial activity (mostly antibiotics some beta-lactamase inhibitors). For each compound, we provide the General Amber Force Field for major species at physiological pH, together analysis interest as extracted from µs-long dynamics simulations in explicit water solution. The include number population structural clusters, flexibility, hydrophobic hydrophilic surfaces, statistics...
Abstract Resistance–nodulation–division efflux pumps play a key role in inherent and evolved multidrug resistance bacteria. AcrB, prototypical member of this protein family, extrudes wide range antimicrobial agents out Although high-resolution structures exist for its conformational fluctuations their putative function are largely unknown. Here, we determine these structural dynamics the presence substrates using hydrogen/deuterium exchange mass spectrometry, complemented by molecular...
Efflux pump avoidance and inhibition are desired properties for the optimization of antibacterial activities against Gram-negative bacteria. However, molecular physicochemical interactions defining interface between compounds efflux pumps remain poorly understood. We identified that correlate with inhibition, predictive similar features in structurally diverse compounds, allow researchers to distinguish substrates, inhibitors, avoiders P. aeruginosa .
Inelastic helium-atom scattering from epitaxial films (2--20 monolayers) of sodium on Cu(001) reveals a large number nearly dispersionless phonon modes whose frequencies depend the thickness and scale as lower harmonics an open-ended organ pipe. These data provide evidence for confined acoustic resonances, corresponding to longitudinal standing waves normal surface with about 20% larger than in bulk.
Recent measurements of the scattering He and Ne atoms at Rh(110) suggest that these two rare-gas measure a qualitatively different surface corrugation: While atom seemingly reflects electron-density undulation substrate surface, potential appears to be anticorrugated. An understanding this perplexing result is lacking. We present density functional theory calculations interaction potentials with Rh(110). find explain why nature probe particles different, which implies topographies their are indeed
We present an experimental and theoretical study of the dispersion curves for vibrations on Si(111)+H(1\ifmmode\times\else\texttimes\fi{}1) surface. In order to explain Rayleigh wave measured by He-atom scattering, we have calculated surface phonon along boundaries irreducible part Brillouin zone in framework bond charge model a slab 22 atomic planes. By fitting force constants related stretching bending frequencies Si-H surface, mode is well reproduced. The good agreement includes rather...