4,188 research outputs found
Socrate immaginario. Excerpts - Don Mus.Ms. 1516 : V (2), strings; RobP 1.48/36
No full textGiovanni PaisielloQuelle: manuscript. - Provenienz: Fürstlich Fürstenbergische Hofbibliothek, DonaueschingenMarituccio mio grazioso | Duetto buffo | Del Sig|r|e D. Giovanni Paesiello. | f.
Covalent docking of selected boron-based serine beta-lactamase inhibitors
No full textAmpC β-lactamase is a hydrolytic enzyme conferring resistance to β-lactam antibiotics in multiple Gram-negative bacteria. Therefore, identification of non-β-lactam compounds able to inhibit the enzyme is crucial for the development of novel antibacterial therapies. In general, AmpC inhibitors have to engage the highly solvent-exposed catalytic site of the enzyme. Therefore, understanding the implications of ligand–protein induced-fit and water-mediated interactions behind the inhibitor-enzyme recognition process is fundamental for undertaking structure-based drug design process. Here, we focus on boronic acids, a promising class of beta-lactamase covalent inhibitors. First, we optimized a docking protocol able to reproduce the experimentally determined binding mode of AmpC inhibitors bearing a boronic group. This goal was pursued (1) performing rigid and flexible docking calculations aiming to establish the role of the side chain conformations; and (2) investigating the role of specific water molecules in shaping the enzyme active site and mediating ligand protein interactions. Our calculations showed that some water molecules, conserved in the majority of the considered X-ray structures, are needed to correctly predict the binding pose of known covalent AmpC inhibitors. On this basis, we formalized our findings in a docking and scoring protocol that could be useful for the structure-based design of new boronic acid AmpC inhibitors
How Computational Chemistry and Drug Delivery Techniques Can Support the Development of New Anticancer Drugs
No full textThe early and late development of new anticancer drugs, small molecules or peptides can be slowed down by some issues such as poor selectivity for the target or poor ADME properties. Computer-aided drug design (CADD) and target drug delivery (TDD) techniques, although apparently far from each other, are two research fields that can give a significant contribution to overcome these problems. Their combination may provide mechanistic understanding resulting in a synergy that makes possible the rational design of novel anticancer based therapies. Herein, we aim to discuss selected applications, some also from our research experience, in the fields of anticancer small organic drugs and peptides
Inactivation of TEM-1 by avibactam (NXL-104): Insights from quantum mechanics/molecular mechanics metadynamics simulations
No full textThe fast and constant development of drug-resistant bacteria represents a serious medical emergence. To overcome this problem, the development of drugs with new structures and modes of action is urgently needed. In this context, avibactam represents a promising, innovative inhibitor of beta-lactamases with a novel molecular structure compared to previously developed inhibitors, showing a promising inhibitory activity toward a significant number of beta-lactamase enzymes. In this work, we studied, at the atomistic level, the mechanisms of formation of the covalent complex between avibactam and TEM-1, an experimentally well-characterized class A beta-lactamase, using classical and quantum mechanics/molecular mechanics (QM/MM) simulations combined with metadynamics. Our simulations provide a detailed structural and energetic picture of the molecular steps leading to the formation of the avibactam/TEM-1 covalent adduct. In particular, they support a mechanism in which the rate-determining step is the water-assisted Glu166 deprotonation by Ser70. In this mechanistic framework, the predicted activation energy is in good agreement with experimental kinetic measurements. Additionally, our simulations highlight the important role of Lys73 in assisting the Ser70 and Ser130 deprotonations. While based on the specific case of the avibactam/TEM-1, the simple protocol we present here can be immediately extended and applied to the study of covalent complex formation in different enzyme-inhibitor pairs. © 2014 American Chemical Society
Le «buone letture». 2. Giovanni Casati
No full textIl saggio è costituito da due parti, la prima delle quali, dedicata alla fondazione della Federazione italiana delle biblioteche circolanti cattoliche, è stata pubblicata nel precedente numero dei «Nuovi Annali», XXVII (2013), pp. 137-163. In questa seconda parte viene delineata la figura intellettuale di Giovanni Casati, che diresse la «Rivista di letture» dal 1912 al 1944, trasformando il periodico della Federazione in una rivista impegnata nella divulgazione della cultura cattolica. A questo impegno militante Casati fece corrispondere un intenso programma editoriale, che trovò espressione nella pubblicazione di saggi letterari, di manuali e opere repertoriali.The study consists of two parts; the first is dedicated to the history of the Federazione italiana delle biblioteche circolanti cattoliche since its foundation (1904) up to 1912 and was published in the previous volume of the «Nuovi Annali », XXVII (2013), pp. 137-163. In this second part, the author outlines the intellectual figure of Giovanni Casati, who directed the «Rivista di letture» from 1912 to 1944, transforming the magazine of the Federation in a journal engaged in the spreading of Catholic culture. To this militant engagement Casati matched an intense publishing program, which found its expression in the publication of literary essays, manuals and reference works
Comico e tragico del diritto nella novellistica italiana: il novelliere di Giovanni Sercambi
No full textNelle novelle di età tardomedievale ed umanistica, a causa del loro carattere fortemente realistico, il diritto ha un posto importante, poiché rappresenta un elemento centrale e ineliminabile della vita della comunità. Il novelliere di Giovanni Sercambi da Lucca non fa eccezione, anche se l’autore non ha una cultura giuridica né s’interessa in modo specifico al diritto. Il presente saggio vuole analizzare sotto tale profilo queste novelle per verificare quale concezione del diritto emerge da esse e come la narrazione ne risulti arricchita.In the late medieval and humanistic novellas, owing to their very realistic character, the right is an important central and inevitable element in community life. Giovanni Sercambi’s novelliere is no exception even if the author lacks a legal culture, nor is specifically interested in right. This essay intends to analyze these novellas under this profile to verify what kind of right they consider and how the stories are enriched
PCSK9-inhibiting compounds
No full textThe invention relates to compounds with formula I: having inhibitory activity against the PCSK9 enzyme. Said compunds can be used, for example, in the prevention and/or treatment of dyslipidaemia
Molecular dynamics simulations of the Salmonella typhi Vi antigenic polysaccharide and effects of the introduction of a zwitterionic motif
No full textA series of hexasaccharides corresponding to the Vi capsular polysaccharide, a polymer of α-(1→4)-galacturonic acid, and analogs containing a zwitterionic motif with various degrees of acetylation at positions 3 have been modeled. When submitted to molecular dynamics simulations in a water box, all the structures visited only two quite restricted regions of the /ψ conformational space both corresponding to extended geometries without any tendency towards supercoiling. The most stable conformation showed a clockwise helix arrangement of substituents on the molecular surface whereas the opposite arrangement was observed for the other conformation. The flexibility of the system and the hydrophobic character of the molecular surface are modulated by the 3-O-acetyl groups that confer rigidity to the system. In the zwitterionic analogs, the introduction of positive charges in the place of the acetamido groups alters the hydrophobicity that can be regained by methylation of the amino groups. The needed molecular flexibility can be obtained by the complete deacetylation at positions 3
Bird presence vegetation complexity data in Melbourne, Australia. Data created in 2018 by Giovanni Carrabs.
No full textBird presence and vegetation complexity data from Melbourne, Australia. Data created for a university thesis project and publication in 2018. Author: Giovanni Carrabs.</p
Concertino - Mus. Hs. 794 : fl (2), vl (2), cor (2), b; C; GroF 877 JenS 80
No full textGiovanni Battista SammartiniQuelle: manuscript. - In der b-Stimme Bezeichnung als "Divertimento". - Am Rand der Stimmen Buchstabe "A". - Tempobezeichnung des zweiten Satzes in fl 1: "non tanto alegro e[?] Grazioso", in cor 1 und cor 2 "Grazioso" und im b: "Non tanto Alegro" (andere Stimmen ohne Tempoangabe). - Beide Sätze sind auch einzeln vorhanden: der erste Satz in D KA Mus. Hs. 783, das Menuett in D KA Mus. Hs. 782 (beide mit anderer Besetzung). - Alte Bleistiftsignatur (durchgestrichen): "119". - Von der Hand des Schreibers 2 stammt nur der Umschlagtitel. - Papier des Umschlags ohne Wasserzeichen. - Auch in I-IBborromeo MS.AU.301 (Stimmen, datiert "del 1753 di Agosto"), dort alernativ auch mit Oboen statt Violinen. - siehe BoggioB 2004[dust cover title:] Concertino | con | Flauti Traversieri | Violini | Corni | è | Basso. | [incipit: fl 1] | del Sig|e: San Martin
- …
