|CCL 18.09.25 Paris Pasteur University International Doctoral Program. Automatic Building of Protein Atomic Models from Cryo-EM Maps using evolutionary coupling data (EMEC: Electron Microscopy and Evolutionary Coupling)|
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Date: Tue Sep 25 09:29:50 2018
Subject: 18.09.25 Paris Pasteur University International Doctoral Program. Automatic Building of Protein Atomic Models from Cryo-EM Maps using evolutionary coupling data (EMEC: Electron Microscopy and Evolutionary Coupling)
Automatic Building of Protein Atomic Models from Cryo-EM Maps using evolutionary coupling data (EMEC: Electron Microscopy and Evolutionary Coupling) The Institut Pasteur has just inaugurated the installation of a new electron microscope equipped with extraordinary capabilities: the new Titan Krios. Cryo-electron microscopy (Cryo-EM) has emerged as a powerful method to obtain electron density maps of protein assemblies. Albeit the incredible resolution of the data obtained by this new generation of microscopes, reconstruction of atomic models from near atomic resolution (3-5 ) cryo-EM maps is still challenging. Several tools developed for X-ray crystallography are widely used to interpret high resolution EM maps (around 3 ), but poorly resolved side-chain densities hamper sequence attribution by automatic procedures at lower resolution. Furthermore, segmentation of EM maps into subunits remains a difficult problem when no structures of these subunits exist, or when conformational changes occur between the isolated and complexed form of the subunits. The aim of the project is to first develop a graph-based method to thread most of the C- trace of the protein backbone into the EM map. The EM density is described as a weighted graph such as the resulting minimum spanning tree encompasses the high density region of the map. A pruning algorithm is then applied to clean the tree and find the most probable positions of the C- atoms, using sidechain density when available, in the form of C- trace fragments. Then the challenge of the approach is to complement the experimental EM maps with contact predictions from sequence co-evolutionary information to: (i) segment correctly the EM maps into individual subunits and thus identify the regions of the different protein partners and (ii) register the protein sequence onto the initial thread found using the graph based approach described previously. Therefore, once the sequence registered, the full-atom protein structure could be modelled onto the density. Once the method developed and implemented, it would be benchmarked onto several Cryo-EM data and applied onto real structural studies of new protein complexes.
The Institut Pasteur in Paris organizes a doctoral program in collaboration with the universities Paris-Descartes, Paris-Diderot, Pierre and Marie Curie, and Paris-Sud, for students holding a master degree or the equivalent in science, medicine and related fields delivered by a university outside of France. In 2009, the Institut Pasteur, the world leading biomedical research institute founded by Louis Pasteur in 1887, inaugurated the Pasteur Paris-University (PPU) international doctoral program in collaboration with several major Parisian science universities for students holding a Master degree (or equivalent) from a university outside of France and who have not worked or resided in France for more than 12 months in the 3 years prior to their recruitment. The 2018-2019 call for enrollment of students in October 2019 is open until November 2nd, 2018. Please go to the dedicated platform: https://ppu.pasteur.fr where you can find the project described (EMEC project) and to submit your application. Deadline for contacting host laboratories: November 2, 2018 Deadline for submitting the application with the host laboratory: November 13, 2018 Interview week: January 29 / February 1, 2019 Contact: guillaume.bouvier^^pasteur.frNOTE THAT E-MAIL ADDRESSES HAVE BEEN MODIFIED!!!
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