Search results for " Simulation"
showing 10 items of 4034 documents
Permeability network model for non-crimp fabrics
2006
In this work a global permeability model is developed and applied to a biaxial Non-crimp stitched fabric (NCF). This model focuses on a detailed meso-scale description of the fabric geometry, which takes into account the local permeability distribution in a fabric due to perturbations of the geometry as well as the geometrical features which arise from the stitching process. It is shown in this work that these features significantly affects the global permeability. The influence of the amount and type of perturbation of a fabric is also studied in this work. It is shown that perturbation of the fabric geometry affect the global permeability but not as much as the stitching process. The mode…
Scalable Constant pH Molecular Dynamics in GROMACS
2022
Molecular dynamics (MD) computer simulations are used routinely to compute atomistic trajectories of complex systems. Systems are simulated in various ensembles, depending on the experimental conditions one aims to mimic. While constant energy, temperature, volume, and pressure are rather straightforward to model, pH, which is an equally important parameter in experiments, is more difficult to account for in simulations. Although a constant pH algorithm based on the λ-dynamics approach by Brooks and co-workers [Kong, X.; Brooks III, C. L. J. Chem. Phys.1996, 105, 2414–2423] was implemented in a fork of the GROMACS molecular dynamics program, uptake has been rather limited, presumably due to…
Structural Determinants for the Mode of Action of Imidazopyridine DS2 at δ-Containing γ-Aminobutyric Acid Type A Receptors
2021
Despite the therapeutic relevance of δ-containing γ-aminobutyric acid type A receptors (GABAARs) and the need for δ-selective compounds, the structural determinants for the mode and molecular site of action of δ-selective positive allosteric modulator imidazo[1,2-a]pyridine DS2 remain elusive. To guide the quest for insight, we synthesized a series of DS2 analogues guided by a structural receptor model. Using a fluorescence-based fluorometric imaging plate reader membrane potential assay, we found that the δ-selectivity and the pharmacological profile are severely affected by substituents in the 5-position of the imidazopyridine core scaffold. Interestingly, the 5-methyl, 5-bromo, and 5-chl…
Inhibition of the Cysteine Protease Human Cathepsin L by Triazine Nitriles: Amide⋅⋅⋅Heteroarene π-Stacking Interactions and Chalcogen Bonding in the …
2016
We report an extensive "heteroarene scan" of triazine nitrile ligands of the cysteine protease human cathepsin L (hCatL) to investigate π-stacking on the peptide amide bond Gly67-Gly68 at the entrance of the S3 pocket. This heteroarene⋅⋅⋅peptide bond stacking was supported by a co-crystal structure of an imidazopyridine ligand with hCatL. Inhibitory constants (Ki ) are strongly influenced by the diverse nature of the heterocycles and specific interactions with the local environment of the S3 pocket. Binding affinities vary by three orders of magnitude. All heteroaromatic ligands feature enhanced binding by comparison with hydrocarbon analogues. Predicted energetic contributions from the ori…
Gene connectivity and enzyme evolution in the human metabolic network
2019
[Background] Determining the factors involved in the likelihood of a gene being under adaptive selection is still a challenging goal in Evolutionary Biology. Here, we perform an evolutionary analysis of the human metabolic genes to explore the associations between network structure and the presence and strength of natural selection in the genes whose products are involved in metabolism. Purifying and positive selection are estimated at interspecific (among mammals) and intraspecific (among human populations) levels, and the connections between enzymatic reactions are differentiated between incoming (in-degree) and outgoing (out-degree) links.
In silico methods for metabolomic and toxicity prediction of zearalenone, α-zearalenone and β-zearalenone.
2020
Zearalenone (ZEA), α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL) (ZEA's metabolites) are co/present in cereals, fruits or their products. All three with other compounds, constitute a cocktail-mixture that consumers (and also animals) are exposed and never entirely evaluated, nor in vitro nor in vivo. Effect of ZEA has been correlated to endocrine disruptor alterations as well as its metabolites (α-ZEL and β-ZEL); however, toxic effects associated to metabolites generated once ingested are unknown and difficult to study. The present study defines the metabolomics profile of all three mycotoxins (ZEA, α-ZEL and β-ZEL) and explores the prediction of their toxic effects proposing an in silico w…
In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges
2020
Flexible spikes The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein enables viral entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor and is a major target for neutralizing antibodies. About 20 to 40 spikes decorate the surface of virions. Turoňová et al. now show that the spike is flexibly connected to the viral surface by three hinges that are well protected by glycosylation sites. The flexibility imparted by these hinges may explain how multiple spikes act in concert to engage onto the flat surface of a host cell. Science, this issue p. 203
Integrazione di celle solari di terza generazione nel vetromattone per la realizzazione di pannelli traslucidi fotovoltaici. Analisi prestazione e st…
2013
L’articolo illustra i primi risultati ottenuti nell’ambito dell’analisi prestazionale del vetromattone fotovoltaico, un prodotto edilizio innovativo derivato dall’integrazione di celle fotovoltaiche di terza generazione (DSSC) nel vetromattone, ideato per la realizzazione di involucri traslucidi energeticamente effi cienti ed “attivi”, in grado di ridurre i consumi energetici degli edifi ci e di produrre, al contempo, energia verde. L’analisi è stata condotta su quattro differenti ipotesi di integrazione. Attraverso simulazioni numeriche si è effettuata una valutazione dell’energia assorbita dagli strati attivi oltre che delle prestazioni ottiche complessive del dispositivo. Lo studio anali…
Defining level A IVIVC dissolution specifications based on individual in vitro dissolution profiles of a controlled release formulation.
2018
Regulatory guidelines recommend that, when a level A IVIVC is established, dissolution specification should be established using averaged data and the maximum difference between AUC and Cmax between the reference and test formulations cannot be greater than 20%. However, averaging data assumes a loss of information and may reflect a bias in the results. The objective of the current work is to present a new approach to establish dissolution specifications using a new methodology (individual approach) instead of average data (classical approach). Different scenarios were established based on the relationship between in vitro-in vivo dissolution rate coefficient using a level A IVIVC of a cont…
Horizontal visibility graphs: exact results for random time series
2009
The visibility algorithm has been recently introduced as a mapping between time series and complex networks. This procedure allows us to apply methods of complex network theory for characterizing time series. In this work we present the horizontal visibility algorithm, a geometrically simpler and analytically solvable version of our former algorithm, focusing on the mapping of random series (series of independent identically distributed random variables). After presenting some properties of the algorithm, we present exact results on the topological properties of graphs associated with random series, namely, the degree distribution, the clustering coefficient, and the mean path length. We sh…