313 research outputs found
Structural flexibility of hyaluronan oligomers as probed by molecular modeling
No full textIn the last few years, molecular modeling studies have been published that are devoted to a better understanding of the structural flexibility of hyaluronan (HA). Further conformational investigations, however, are needed on this polysaccharide, such as the application of statistical methods to perform enhanced one-step conformational analyses of its subunits. Moreover, the adjustment of assisted model building and energy refinement (AMBER) force field could provide the appropriate computational tool to study the interactions of HA and its derivatives with proteins. The present paper reports a combined Monte Carlo (MC) and molecular dynamics (MD) approach applied to the conformational study of HA, using an adjusted version of AMBER force field and the generalized Born solvent-accessible surface area (GB/SA) continuum solvation model. The MC approach turned out to be extremely effective to outline a conformational survey of the disaccharides constituting HA. Complete sets of conformations of the monomers were provided for the first time, some of which had never been predicted. MD technique, integrating the MC results, correctly reproduced the unusual stiffness of HA and predicted the existence of a minor skew-boat conformation of the β-D-glucuronic moiety. The computational approach, as a whole, improved the comprehension of the dynamic behavior of HA and offered a clear causal explanation of the relative dynamics of the glycosidic linkages
Valori della persone e modelli di tutela contro i rischi ambientali e genotossici. Esperienze a confronto
No full textBEPU analysis of a passive decay heat removal system with RELAP5/MOD3.3 and RELAP5-3D
No full textPassive safety systems are currently implemented or under consideration in several advanced nuclear plants. In the Best-Estimate Plus Uncertainty (BEPU) approach it is fundamental to qualify Best-Estimate thermal-hydraulic system codes and models for the phenomena typical of passive systems and to quantify the uncertainty of calculations. In the present paper, through RELAP5/MOD3.3 and RELAP5-3D codes, thermal-hydraulic analyses were carried out and the obtained results compared against the experimental data collected in the experimental test facility PERSEO. For the present analysis, Test 7 Part 2, conducted at the nominal primary pressure of 7 MPa, has been selected. An accuracy evaluation has been performed on the reference calculation carried out with the two codes. For the accuracy evaluation both a qualitative and quantitative approach have been considered. The uncertainty of both calculations has been quantified by means of the probabilistic method of propagation of input uncertainties. Uncertain input parameters have been selected considering initial and boundary conditions, physical parameters and model uncertainties. The Uncertainty Analysis has been carried out through the RAVEN framework developed by Idaho National Laboratory. Additionally, regression and correlation indices have been used to characterize the importance of the selected uncertain input parameters for the selected Figure Of Merit. The effect of sampling methodologies on the results has also been evaluated
Current updates on naturally occurring compounds recognizing sars-cov-2 druggable targets
No full textThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified in China as the etiologic agent of the recent COVID-19 pandemic outbreak. Due to its high transmissibil-ity, this virus quickly spread throughout the world, causing considerable health issues. The scientific community exerted noteworthy efforts to obtain therapeutic solutions for COVID-19, and new scientific networks were constituted. No certified drugs to efficiently inhibit the virus were identified, and the development of de-novo medicines requires approximately ten years of research. Therefore, the repurposing of natural products could be an effective strategy to handle SARS-CoV-2 infection. This review aims to update on current status of the natural occurring compounds recognizing SARS-CoV-2 druggable targets. Among the clinical trials actually recruited, some natural compounds are ongoing to examine their potential role to prevent and to treat the COVID-19 infection. Many natural scaffolds, including alkaloids, terpenes, flavonoids, and benzoquinones, were investigated by in-silico, in-vitro, and in-vivo approaches. Despite the large data set obtained by a computational approach, experimental evidences in most cases are not available. To fill this gap, further efforts to validate these results are required. We believe that an accurate investigation of naturally occurring compounds may provide insights for the potential treatment of COVID-19 patients
Atropisomerism in Hindered Naphtyl Sulfones Investigated by Dynamic NMR and Dynamic HPLC Tecniques.
No full textInside perspective of the synthetic and computational toolbox of JAK inhibitors: Recent updates
No full textThe mechanisms of inflammation and cancer are intertwined by complex networks of signaling pathways. Dysregulations in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway underlie several pathogenic conditions related to chronic inflammatory states, autoimmune diseases and cancer. Historically, the potential application of JAK inhibition has been thoroughly explored, thus triggering an escalation of favorable results in this field. So far, five JAK inhibitors have been approved by the Food and Drug Administration (FDA) for the treatment of different diseases. Considering the complexity of JAK-depending processes and their involvement in multiple disorders, JAK inhibitors are the perfect candidates for drug repurposing and for the assessment of multitarget strategies. Herein we reviewed the recent progress concerning JAK inhibition, including the innovations provided by the release of JAKs crystal structures and the improvement of synthetic strategies aimed to simplify of the industrial scale-up
The betaI/betaIII tubulin isoforms and their complexes with antimitotic agents: docking and molecular dynamics studies.
No full textUnusually high enantioselectivity in high-performance liquid chromatography using cellulose tris(4-methylbenzoate) as a chiral phase
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