1,721,159 research outputs found
Catalytic arylation of carbon-carbon double bond followed by nitrogen- or oxygen-cyclization
No full textin onore del Prof. M. Vol'pi
Peserico, A. Germani, P. Sanese, V. Di Virgilio, V. Grossi, M. Nicola, A.J.M. Barbosa, A. Del Rio, C. Simone
No full text
Realization theorems for categories of graded modules over semigroup-graded rings
No full textWe present a collection of finitely generated projective generators for the category of graded modules over a unital semigroup-graded ring. Consequences of the existence of such a collection, as well as other module-theoretic results, will arise from more general constructions involving TTF classes inside Grothendieck categories. For instance, we obtain a description of the category of graded modules whose support lies within a given subset of the semìgroup. © 1994, Taylor & Francis Group, LLC. All rights reserved
El niño, un creativo a toda costa
No full textNelle società puerocentriche prevale l'immagine di una infanzia le cui capacità creative più che liberamente espresse sono metodicamente conltivate attraverso processi di socializzazione tendenzialmente omologant
Fast and accurate predictions of relative binding free energies using MM-PBSA and MM-GBSA
No full textIn the drug discovery process, accurate methods of computing the affinity of small molecules with a biological target are strongly needed. This is particularly true for molecular docking and virtual screening methods, which use approximated scoring functions and struggle in estimating binding energies in correlation with experimental values. Among the various methods, MM-PBSA and MM-GBSA are emerging as useful and effective approaches. Although these methods are typically applied to large collections of equilibrated structures of protein-ligand complexes sampled during molecular dynamics in water, the possibility to reliably estimate ligand affinity using a single energy-minimized structure and implicit solvation models has not been explored in sufficient detail. Herein, we thoroughly investigate this hypothesis by comparing different methods for the generation of protein-ligand complexes and diverse methods for free energy prediction for their ability to correlate with experimental values. The methods were tested on a series of structurally diverse inhibitors of Plasmodium falciparum DHFR with known binding mode and measured affinities. The results showed that correlations between MM-PBSA or MM-GBSA binding free energies with experimental affinities were in most cases excellent. Importantly, we found that correlations obtained with the use of a single protein-ligand minimized structure and with implicit solvation models were similar to those obtained after averaging over multiple MD snapshots with explicit water molecules, with consequent save of computing time without loss of accuracy. When applied to a virtual screening experiment, such an approach proved to discriminate between true binders and decoy molecules and yielded significantly better enrichment curve
Importations et productions locales de la haute Etrurie tyrrhénienne, de la période de la romanisation jusqu' au VIème siècle apr. J.- C. Un exemple d'étude archéométrique
No full textActivity prediction and structural insights of Extracellular Signal-Regulated Kinase 2 inhibitors with molecular dynamics simulations
No full textA computational application to predict, probe and interpret the activities of a series of congeneric compounds inhibiting extracellular signal-regulated kinase 2 protein kinase is presented. The study shows that molecular dynamics coupled with molecular mechanics Poisson-Boltzmann solvent accessible surface area free energy estimation is a suitable tool for investigating the experimental binding activities of ligands to protein kinases. Computed and experimental binding activities were found to be significantly correlated. Moreover, the interpretation of the X-ray co-crystal structure in conjunction with computational results shows that the hinge region of the protein insure the principal binding site via multiple hydrogen bonding interactions, whereas fine-modulation of biological activities along the series is accomplished through the combination of weak and strong interactions that compete with water. These are located in the substituent moieties of the ligands interfacing with the DFG motif, the sugar region and the hydrophobic pocket of extracellular signal-regulated kinase 2. The study suggests that a wider interaction framework that is well beyond the hinge region is required to predict and rationalize at molecular level the experimental biological activities of congeneric compound series
Assessing protein kinase selectivity with molecular dynamics and MM-PBSA binding free energy calculations.
No full textAn application of molecular dynamics and molecular mechanics Poisson-Boltzmann surface area techniques to the prediction of protein kinase inhibitor selectivity is presented. A highly active and selective ERK2 inhibitor was placed in equivalent orientations in five different protein kinases (SRC, LCK, GSK3, JNK3 and Aurora-A). Binding free energies were then computed with the molecular mechanics Poisson-Boltzmann surface area approach using 15 nanosecond fully solvated molecular dynamics trajectories of the corresponding protein-ligand complexes. The results show correlation with experimentally determined selectivities and provide useful insights into the underlying structural determinants for selectivity
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