MDM2 Case Study: Computational Protocol Utilizing Protein Flexibility Improves Ligand Binding Mode Predictions

Recovery of the P53 tumor suppressor pathway via small molecule inhibitors of onco-protein MDM2 highlights the critical role of computational methodologies in targeted cancer therapies. Molecular docking programs in particular, provide a quantitative ranking of predicted binding geometries based on binding free energy allowing for the screening of large chemical libraries in search of lead compounds for cancer therapeutics. This study found improved binding mode predictions of medicinal compounds to MDM2 using the popular docking programs AutoDock and AutoDock Vina, while adopting a rigid-ligand/flexible-receptor protocol. Crystal structures representing small molecule inhibitors bound to MDM2 were selected and a total of 12 rotatable bonds was supplied to each complex and distributed systematically between the ligand and binding site residues. Docking results were evaluated in terms of the top ranked binding free energy and corresponding RMSD values from the experimentally known binding site. Results show lowest RMSD values coincide with a rigid ligand, while the protein retained the majority of flexibility. This study suggests the future implementation of a rigid-ligand/flexible-receptor protocol may improve accuracy of high throughput screenings of potential cancer drugs targeting the MDM2 protein, while maintaining manageable computational costs

Fixed Points and Attractors of Reactantless and Inhibitorless Reaction Systems

Reaction systems are discrete dynamical systems that model biochemical processes in living cells using finite sets of reactants, inhibitors, and products. We investigate the computational complexity of a comprehensive set of problems related to the existence of fixed points and attractors in two constrained classes of reaction systems, in which either reactants or inhibitors are disallowed. These problems have biological relevance and have been extensively studied in the unconstrained case; however, they remain unexplored in the context of reactantless or inhibitorless systems. Interestingly, we demonstrate that although the absence of reactants or inhibitors simplifies the system's dynamics, it does not always lead to a reduction in the complexity of the considered problems.Comment: 29 page

La spontanéité des émotions mise à l’épreuve sur internet : exprimer, susciter, manipuler

Der Artikel enthält das Abstract ausschließlich in englischer und französischer Sprache.Due to the development of the computer-mediated communication, the expression of emotions has undergone significant changes. This paper proposes à linguistic analysis of the verbalisation of emotions on the Internet. The goal was to examine the way the expression of emotions can be exploited by the speaker. Therefore, the study was conducted on a propagandist discourse available on the Internet. More particularly, Dabiq and Dar al-Islam, the official online magazines published by the Islamic State, constituted the corpus of this analysis. This way, it was possible to investigate how emotions, which are spontaneous by nature, become carefully formulated productions.Face au développement de la communication médiée par les réseaux, l’expression des émotions a subi d’importants changements. Cette contribution propose une analyse linguistique de l’expression des émotions sur internet. Afin d’examiner la façon dont l’expression des émotions peut être exploitée par l’énonciateur, l’étude a porté sur un discours propagandiste diffusé sur internet. Plus particulièrement, Dabiq et Dar al-Islam, les deux revues publiées en ligne par l’État islamique, ont constitué notre corpus. Il a été ainsi possible de voir comment les émotions, par nature spontanées, se traduisent ici en productions soigneusement formulées

Economic and social impacts of the media

openLa presente tesi si propone di esaminare il ruolo dei mass media nell'odierna società, concentrandosi sui loro impatti sociali ed economici. Saranno analizzate le caratteristiche distintive dei mass media, evidenziando il loro potenziale di influenza sulla società attraverso la diffusione di informazioni e il loro impatto sulle preferenze e il tempo di utilizzo delle persone. Inoltre, esamineremo l'effetto di sostituzione, ovvero la scelta tra l'esposizione ai mass media e un’attività alternativa, concludendo con un'analisi della correlazione tra mass media e edutainment. Successivamente esploreremo le implicazioni dei mass media sull'economia familiare, sull'educazione e sull'ambiente, nonché sul consumo e il risparmio delle risorse. Infine saranno esaminate l'impatto sociale dei mass media, mettendo in evidenza le loro influenze su fenomeni quali la fertilità, la migrazione, il crimine e la salute. Questa ricerca fornisce un quadro completo dell'importante ruolo dei mass media nella società contemporanea, evidenziando come essi siano in grado di plasmare e influenzare aspetti cruciali della vita delle persone e della comunità, spaziando dall'informazione all'educazione, dall'ambiente all'economia, e influenzando direttamente o indirettamente una vasta gamma di questioni sociali