10 simple rules to create a serious game, illustrated with examples from structural biology

Serious scientific games are games whose purpose is not only fun. In the field of science, the serious goals include crucial activities for scientists: outreach, teaching and research. The number of serious games is increasing rapidly, in particular citizen science games, games that allow people to produce and/or analyze scientific data. Interestingly, it is possible to build a set of rules providing a guideline to create or improve serious games. We present arguments gathered from our own experience ( Phylo , DocMolecules , HiRE-RNA contest and Pangu) as well as examples from the growing literature on scientific serious games

Middle East - North Africa and the millennium development goals : implications for German development cooperation

          Closed-loop controlled combustion is a promising technique to improve the overall performance of internal combustion engines and Diesel engines in particular. In order for this technique to be implemented some form of feedback from the combustion process is required. The feedback signal is processed and from it combustionrelated parameters are computed. These parameters are then fed to a control process which drives a series of outputs (e.g. injection timing in Diesel engines) to control their values. This paper’s focus lies on the processing and computation that is needed on the feedback signal before this is ready to be fed to the control process as well as on the electronics necessary to support it. A number of feedback alternatives are briefly discussed and for one of them, the in-cylinder pressure sensor, the CA50 (crank angle in which the integrated heat release curve reaches its 50% value) and the IMEP (Indicated Mean Effective Pressure) are identified as two potential control variables. The hardware architecture of a system capable of calculating both of them on-line is proposed and necessary feasibility size and speed considerations are made by implementing critical blocks in VHDL targeting a flash-based Actel ProASIC3 automotive-grade FPGA

MANHaptic: A Haptic Adaptive Method for Precise Manipulation, Assembly \and Navigation

International audienceno abstrac

A Molecular Perspective on Mitochondrial Membrane Fusion: From the Key Players to Oligomerization and Tethering of Mitofusin

Mitochondria are dynamic organelles characterized by an ultrastructural organization which is essential in maintaining their quality control and ensuring functional efficiency. The complex mitochondrial network is the result of the two ongoing forces of fusion and fission of inner and outer membranes. Understanding the functional details of mitochondrial dynamics is physiologically relevant as perturbations of this delicate equilibrium have critical consequences and involved in several neurological disorders. Molecular actors involved in this process are large GTPases from the dynamin-related protein family. They catalyze nucleotide-dependent membrane remodeling and are widely conserved from bacteria to higher eukaryotes. Although structural characterization of different family members has contributed in understanding molecular mechanisms of mitochondrial dynamics in more detail, the complete structure of some members as well as the precise assembly of functional oligomers remains largely unknown. As increasing structural data become available, the domain modularity across the dynamin superfamily emerged as a foundation for transfering the knowledge towards less characterized members. In this review, we will first provide an overview of the main actors involved in mitochondrial dynamics. We then discuss recent example of computational methodologies for the study of mitofusin oligomers, and present how the usage of integrative modeling in conjunction with biochemical data can be an asset in progressing the still challenging field of membrane dynamics

Outer membrane proteins: comparing X-ray and NMR structures by MD simulations in lipid bilayers.

The structures of three bacterial outer membrane proteins (OmpA, OmpX and PagP) have been determined by both X-ray diffraction and NMR. We have used multiple (7 x 15 ns) MD simulations to compare the conformational dynamics resulting from the X-ray versus the NMR structures, each protein being simulated in a lipid (DMPC) bilayer. Conformational drift was assessed via calculation of the root mean square deviation as a function of time. On this basis the 'quality' of the starting structure seems mainly to influence the simulation stability of the transmembrane beta-barrel domain. Root mean square fluctuations were used to compare simulation mobility as a function of residue number. The resultant residue mobility profiles were qualitatively similar for the corresponding X-ray and NMR structure-based simulations. However, all three proteins were generally more mobile in the NMR-based than in the X-ray simulations. Principal components analysis was used to identify the dominant motions within each simulation. The first two eigenvectors (which account for >50% of the protein motion) reveal that such motions are concentrated in the extracellular loops and, in the case of PagP, in the N-terminal alpha-helix. Residue profiles of the magnitude of motions corresponding to the first two eigenvectors are similar for the corresponding X-ray and NMR simulations, but the directions of these motions correlate poorly reflecting incomplete sampling on a approximately 10 ns timescale

Stabilité et structure des canaux d'eau artificielles supramoléculaires auto-organisés adaptatifs dans les bicouches lipidiques

International audienceNanopores that efficiently and selectively transport water have been intensively studied at the nanoscale level. A key challenge relates to linking the nanoscale to the compound's macroscopic properties, which are hardly accessible at the smaller scale. Here we numerically investigate the influence of varying the dimensions of a self-assembled Imidazole I-quartet (I4) aggregate in lipid bilayers on the water permeation properties of these highly packed water channels. Quantitative transport studies reveal that water pathways in I4 crystal-like packing are not affected by small scaling factors, despite non-uniform contributions between central channels shielded from the bilayer and lateral, exposed channels. The permeation rate computed in simulations overestimates the experimental value by an order of magnitude, yet these in silico properties are very dependent on the force field parameters. The diversity of observed water pathways in such a small-scale in silico experiment yields some insights into modifying the current molecular designs in order to considerably improve water transport in scalable membranes.Les nanopores qui transportent de l'eau de manière efficace et sélective ont été étudiées de manière intensive au niveau nanométrique. Un défi majeur consiste à relier la nanométrie aux propriétés macroscopiques du composé, qui ne sont guère accessibles à plus petite échelle. Ici, nous étudions numériquement l'influence de la variation des dimensions d'un agrégat d'imidazole I-quartet (I4) auto-assemblé dans des bicouches lipidiques sur les propriétés de perméation de l'eau de ces canaux d'eau très emballés. Des études quantitatives sur le transport révèlent que les voies d'eau dans les emballages cristallins I4 ne sont pas affectées par de petits facteurs de mise à l'échelle, malgré des contributions non uniformes entre les canaux centraux protégés du bicouche et les canaux latéraux exposés. Le taux de perméation calculé dans les simulations surestime la valeur expérimentale d'un ordre de grandeur, mais ces propriétés in silico dépendent beaucoup des paramètres du champ de force. La diversité des voies navigables observées dans une telle expérience in silico à petite échelle donne un aperçu de la modification des conceptions moléculaires actuelles afin d'améliorer considérablement le transport de l'eau dans les membranes évolutives

Molecular Visualization of Computational Biology Data: A Survey of Surveys

International audienceVisualizations for computational biology have been developing for over 50 years. With recent advances in both computational biology and computer graphics techniques, these fields have witnessed rapid technological advances in the last decade. Thus, coping with the large number of scientific articles from both fields is a challenging task. Furthermore, there remains a gap between the two communities of visualization and computational biology, resulting in additional challenges to bridge the divide. A team of computational biology and visualization scientists attempts to address these challenges by presenting unified state-of-the-art reviews from both communities. We apply a variety of data-driven analysis to highlight links or differences between studies from both communities. This approach facilitates the identification of present and future challenges in visualizing and analyzing computational biology data. It offers a distinctive step forward in managing the literature on visualization of molecular dynamics and related simulation approaches

String method solution of the gating pathways for a pentameric ligand-gated ion channel

International audiencePentameric ligand-gated ion channels control synaptic neurotransmission by converting chemical signals into electrical signals. Agonist binding leads to rapid signal transduction via an allosteric mechanism, where global protein conformational changes open a pore across the nerve cell membrane. We use all-atom molecular dynamics with a swarm-based string method to solve for the minimum free-energy gating pathways of the proton-activated bacterial GLIC channel. We describe stable wetted/open and dewetted/closed states, and uncover conformational changes in the agonist-binding extracellular domain, ion-conducting transmembrane domain, and gating interface that control communication between these domains. Transition analysis is used to compute free-energy surfaces that suggest allosteric pathways; stabilization with pH; and intermediates, including states that facilitate channel closing in the presence of an agonist. We describe a switching mechanism that senses proton binding by marked reorganization of subunit interface, altering the packing of β-sheets to induce changes that lead to asynchronous pore-lining M2 helix movements. These results provide molecular details of GLIC gating and insight into the allosteric mechanisms for the superfamily of pentameric ligand-gated channels