Sampling of the conformational landscape of small proteins with Monte Carlo methods

Computer simulation provides an increasingly realistic picture of large-scale conformational change of proteins, but investigations remain fundamentally constrained by the femtosecond timestep of molecular dynamics simulations. For this reason, many biologically interesting questions cannot be addressed using accessible state-of-the-art computational resources. Here, we report the development of an all-atom Monte Carlo approach that permits the modelling of the large-scale conformational change of proteins using standard off-the-shelf computational hardware and standard all-atom force fields. We demonstrate extensive thermodynamic characterization of the folding process of the α-helical Trp-cage, the Villin headpiece and the β-sheet WW-domain. We fully characterize the free energy landscape, transition states, energy barriers between different states, and the per-residue stability of individual amino acids over a wide temperature range. We demonstrate that a state-of-the-art intramolecular force field can be combined with an implicit solvent model to obtain a high quality of the folded structures and also discuss limitations that still remain

An Implicit Solvent Model for Biomolecular Monte Carlo Simulations

Implizite Lösungsmittelmodelle in biomolekularen Simulationen beschreiben die physikalischen Wechselwirkungen zwischen den Biomolekülen, z. B. Proteine, und deren Umgebung. In dieser Dissertation wurden neue Modelle entwickelt, die eine genauere und effizientere Beschreibung dieser Wechselwirkungen erlauben. Eines dieser Modelle wurde erfolgreich angewandt, um den komplexen Faltungsprozess einen kleinen Proteins mit Hilfe von Monte-Carlo-Methoden zu studieren

Comment flirter avec la modernité pour conforter son identité : Projet éducatif d’une communauté métisse au Manitoba

En 1994, une école francophone était créée au sein de la communauté métisse de Saint-Laurent (Manitoba). La création de cette école institutionnalisait la division préexistante entre Métis francophones et Métis anglophones. Cet article propose une analyse du projet éducatif mis au point par l’école métisse francophone. Selon l’auteur, ce projet est à la fois culturel, destiné à préserver la langue vernaculaire des Métis, le mitchif, mais aussi politique, destiné à redonner aux Métis la capacité de définir eux-mêmes leur futur. Sur le plan pédagogique, le projet scolaire tente d’intégrer savoirs modernes et savoirs autochtones et cherche à créer des liens entre les aînés et les jeunes ainsi qu’entre l’école et la communauté. Ses fondements théoriques et idéologiques s’inscrivent dans un courant qui traverse aujourd’hui un certain nombre de collectivités autochtones. La particularité du projet réside dans une alliance stratégique entre la communauté métisse et les Franco-Manitobains, et par-delà cette alliance, dans une tentative de relier la communauté aux réseaux globaux, via la francophonie.In 1994, a francophone school was established in the heart of the Métis community of St Laurent, Manitoba. The creation of the school institutionalized a pre-existing divide between the Francophone and Anglophone Métis populations. This article provides an analysis of the educational project developed by the Francophone Métis community. We will see that the project is a cultural and political enterprise, which aims both to preserve the traditional vernacular of the Métis, the Michif language, as well as to reclaim the community’s capacity for self-determination. The pedagogical model of the project integrates elements of modern knowledge and traditional Aboriginal knowledge, and aims to strengthen social ties both between elders and youth and between the school and the larger community. The theoretical foundations of this model are part of a trend observable in a number of Aboriginal communities. However, the specific feature of the project is in the strategic alliance forged between the Métis and Franco-Manitoban communities and, beyond this alliance, in attempts at connecting the Métis with global francophone networks

Comment flirter avec la modernité pour conforter son identité. Projet éducatif d'une communauté métisse au Manitoba

International audienceIn 1994, a francophone school was esta- blished in the heart of the Métis community of St Laurent, Manitoba. The creation of the school institutionalized a pre-existing divide between the Francophone and Anglophone Métis populations. This article provides an analysis of the educational project developed by the Francophone Métis community. We will see that the project is a cultural and political enterprise, which aims both to preserve the traditional vernacular of the Métis, the Michif language, as well as to reclaim the community's capacity for selfdetermination. The pedagogical model of the project integrates elements of modern knowledge and traditional Aboriginal knowledge, and aims to strengthen social ties both between elders and youth and between the school and the larger community. The theoretical foundations of this model are part of a trend observable in a number of Aboriginal communities. However, the specific feature of the project is in the strategic alliance forged between the Métis and Franco-Manitoban communities and, beyond this alliance, in attempts at connecting the Métis with global francophone networks.En 1994, une école francophone était créée au sein de la communauté métisse de Saint-Laurent (Manitoba). La création de cette école institutionnalisait la division préexistante entre Métis francophones et Métis anglophones. Cet article propose une analyse du projet éducatif mis au point par l'école métisse francophone. Selon les auteurs, ce projet est à la fois culturel, destiné à préserver la langue vernaculaire des Métis, le mitchif, mais aussi politique, destiné à redonner aux Métis la capacité de définir eux-mêmes leur futur. Sur le plan pédagogique, le projet scolaire tente d'intégrer savoirs modernes et savoirs autochtones et cherche à créer des liens entre les aînés et les jeunes ainsi qu'entre l'école et la communauté. Ses fondements théoriques et idéologiques s'inscrivent dans un courant qui traverse aujourd'hui un certain nombre de collectivités autochtones. La particularité du projet réside dans une alliance stratégique entre la communauté métisse et les Franco-Manitobains, et par-delà cette alliance, dans une tentative de relier la communauté aux réseaux globaux, via la francophonie

PowerBorn: A Barnes–Hut Tree Implementation for Accurate and Efficient Born Radii Computation

Implicit solvent models are one of the standard tools in computational biophysics. While Poisson–Boltzmann methods offer highly accurate results within this framework, generalized Born models have been used due to their higher computational efficiency in many (bio)­molecular simulations, where computational power is a limiting factor. In recent years, there have been remarkable advances to reduce some deficiencies in the generalized Born models. On the other hand, these advances come at an increased computational cost that contrasts the reasons for choosing generalized Born models over Poisson–Boltzmann methods. To address this performance issue, we present a new algorithm for Born radii computation, one performance critical part in the evaluation of generalized Born models, which is based on a Barnes–Hut tree code scheme. We show that an implementation of this algorithm provides accurate Born radii and polar solvation free energies in comparison to Poisson–Boltzmann computations, while delivering up to an order of magnitude better performance over existing, similarly accurate methods. The C++ implementation of this algorithm will be available at http://www.int.kit.edu/nanosim/

PowerBorn: A Barnes–Hut Tree Implementation for Accurate and Efficient Born Radii Computation

Implicit solvent models are one of the standard tools in computational biophysics. While Poisson–Boltzmann methods offer highly accurate results within this framework, generalized Born models have been used due to their higher computational efficiency in many (bio)­molecular simulations, where computational power is a limiting factor. In recent years, there have been remarkable advances to reduce some deficiencies in the generalized Born models. On the other hand, these advances come at an increased computational cost that contrasts the reasons for choosing generalized Born models over Poisson–Boltzmann methods. To address this performance issue, we present a new algorithm for Born radii computation, one performance critical part in the evaluation of generalized Born models, which is based on a Barnes–Hut tree code scheme. We show that an implementation of this algorithm provides accurate Born radii and polar solvation free energies in comparison to Poisson–Boltzmann computations, while delivering up to an order of magnitude better performance over existing, similarly accurate methods. The C++ implementation of this algorithm will be available at http://www.int.kit.edu/nanosim/

PowerBorn: A Barnes–Hut Tree Implementation for Accurate and Efficient Born Radii Computation

Implicit solvent models are one of the standard tools in computational biophysics. While Poisson–Boltzmann methods offer highly accurate results within this framework, generalized Born models have been used due to their higher computational efficiency in many (bio)­molecular simulations, where computational power is a limiting factor. In recent years, there have been remarkable advances to reduce some deficiencies in the generalized Born models. On the other hand, these advances come at an increased computational cost that contrasts the reasons for choosing generalized Born models over Poisson–Boltzmann methods. To address this performance issue, we present a new algorithm for Born radii computation, one performance critical part in the evaluation of generalized Born models, which is based on a Barnes–Hut tree code scheme. We show that an implementation of this algorithm provides accurate Born radii and polar solvation free energies in comparison to Poisson–Boltzmann computations, while delivering up to an order of magnitude better performance over existing, similarly accurate methods. The C++ implementation of this algorithm will be available at http://www.int.kit.edu/nanosim/