On the Importance of Atomic Fluctuations, Protein Flexibility, and Solvent in Ion Permeation

Proteins, including ion channels, often are described in terms of some average structure and pictured as rigid entities immersed in a featureless solvent continuum. This simplified view, which provides for a convenient representation of the protein's overall structure, incurs the risk of deemphasizing important features underlying protein function, such as thermal fluctuations in the atom positions and the discreteness of the solvent molecules. These factors become particularly important in the case of ion movement through narrow pores, where the magnitude of the thermal fluctuations may be comparable to the ion pore atom separations, such that the strength of the ion channel interactions may vary dramatically as a function of the instantaneous configuration of the ion and the surrounding protein and pore water. Descriptions of ion permeation through narrow pores, which employ static protein structures and a macroscopic continuum dielectric solvent, thus face fundamental difficulties. We illustrate this using simple model calculations based on the gramicidin A and KcsA potassium channels, which show that thermal atomic fluctuations lead to energy profiles that vary by tens of kcal/mol. Consequently, within the framework of a rigid pore model, ion-channel energetics is extremely sensitive to the choice of experimental structure and how the space-dependent dielectric constant is assigned. Given these observations, the significance of any description based on a rigid structure appears limited. Creating a conducting channel model from one single structure requires substantial and arbitrary engineering of the model parameters, making it difficult for such approaches to contribute to our understanding of ion permeation at a microscopic level

Assembly and Architecture of Gram-Positive and -Negative Cell Walls

The cell wall, a porous mesh-like structure, provides shape and physical protection for bacteria. At the atomic level, it is composed of peptidoglycan (PG), a polymer of stiff glycan strands cross-linked by short, flexible peptides. However, at the mesoscale, multiple models for the organization of PG have been put forth, distinguished by glycan strands parallel to the cell surface (the so-called "layered'' model) or perpendicular (the “scaffold” model). To test these models, and to resolve the mechanical properties of PG, we have built and simulated at an atomic scale patches of both Gram-positive and negative cell walls in different organizations up to 50 nanometers in size. In the case of Gram-positive PG, molecular dynamics simulations of the layered model are found to elucidate the mechanisms behind a distinct curling effect observed in three-dimensional electron cryo-tomography images of fragmented cell walls. For Gram-negative PG, simulations of patches with different average-glycan-strand lengths reveal an anisotropic elasticity, in good agreement with atomic-force microscopy experiments. Insights from the simulations reveal how mesoscopic and macroscopic properties of a ubiquitous bacterial ultrastructure arise from its atomic-scale interactions and organization

Modèles génératif et discriminant en analyse syntaxique : expériences sur le corpus arboré de Paris 7

International audienceNous présentons une architecture pour l'analyse syntaxique en deux étapes. Dans un premier temps un analyseur syntagmatique construit, pour chaque phrase, une liste d'analyses qui sont converties en arbres de dépendances. Ces arbres sont ensuite réévalués par un réordonnanceur discriminant. Cette méthode permet de prendre en compte des informations auxquelles l'analyseur n'a pas accès, en particulier des annotations fonction- nelles. Nous validons notre approche par une évaluation sur le corpus arboré de Paris 7. La seconde étape permet d'améliorer significativement la qualité des analyses retournées, quelle que soit la métrique utilisée