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Section: Partnerships and Cooperations
International Initiatives
Inria Associate Teams Not Involved in an Inria International Labs
FlexMol
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International Partner (Institution - Laboratory - Researcher):
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Molecular flexibility is essential to link structure and function of many biological macromolecules. Changes in protein conformation play a vital role in biochemical processes, from biopolymer synthesis to membrane transport. Many proteins can drastically alter their architecture and display considerable interdomain flexibility, as found in their 3D structures. For example, proteins rely on flexibility to respond to environmental changes, ligand binding and chemical modifications. Also, protein flexibility is tightly bound to their stability and is fundamental for drugs to exert biological effects.
Thus, one of the main challenges in the field of computational structural biology is to predict and explain molecular flexibility and corresponding conformational changes. For example, currently there are no methods that can reliably predict structural changes in proteins upon their binding. However, these are crucial to predict the structure of protein complexes with large conformational changes upon binding. To give another example, flexibility of the protein binding pocket is the major hurdle in reliable prediction of protein-ligand interactions for computer-aided drug design. Finally, intrinsic flexibility of macromolecules is nowadays the limiting factor for high-resolution experimental structure determination.
The partners of this associate team proposal comprise world-leading teams working with sound mathematical representations and techniques in the field of structural bioinformatics. These include spherical harmonics, normal modes analysis, high-order fast Fourier transforms, and more. The partners have very similar interests, but complimentary expertise. The goal of this collaboration is to mutually explore novel computational techniques for emerging problems in structural biology and bioinformatics related to molecular flexibility. This problem can be tackled at different scales. Large-scale flexibility of macromolecules can be efficiently described using collective coordinates. We will try to represent these in polynomial spaces, such that a practical flexible docking method can be based on this representation. Other applications include 3D shape reconstruction and scattering problems. Local molecular flexibility can be modelled using various techniques, including robotics-inspired methods, fragment libraries, etc. Here, our goal will be to rapidly sample the conformational space, and to construct a potential energy function applicable to flexible molecules. The ultimate goal of the project is to combine multiple levels of representation of molecular flexibility together. The project outcome will be built around innovative computer-aided drug-design algorithm with applications to prediction and computational design of important pharmaceutical targets such as antibodies.
Inria International Partners
Declared Inria International Partners : BIOTOOLS
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Title: Novel Computational Tools for Structural Bioinformatics
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International Partner (Institution - Laboratory - Researcher):
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Abstract : The general scientific objectives of the forthcoming collaboration are the new developments of computational tools for structural bioinformatics. In particular, we plan to collaborate on several subjects: 1. Development of tractable approximations for intractable combinatorial problems in structural biology. 2. Development of new computational tools for scattering experiments. 3. Machine learning for structural bioinformatics.
Informal International Partners
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University of Stony Brook, lab of Dima Kozakov (USA). We have been collaborating on the development of novel protein docking methods.
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University of Vilnius, department of Bioinformatics (Lithuania). We have been collaborating on the development of novel protein docking methods.
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KU Copenhagen (Denmark), department of Chemistry. We collaborated on the integrative structural biology approaches.
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Francis Crick Institute, London (UK), Biomolecular Modelling Laboratory. We collaborate on the development of flexible protein docking methods.
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University of Oslo. Ongoing collaboration on modeling protein systems guided by small-angle Xray and neutron small-angle scattering.
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University of Bergen, Norway. Ongoing collaboration on novel methods for normal mode analysis of protein structures.
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Nagoya University and RIKEN Center for Computational Science, Kobe, Japan. We collaborated on novel algorithms for scattering methods.
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University of Kansas, bioinformatics unit, USA. We have been collaborating on modeling protein-protein interactions.
Participation in Other International Programs
Our team has obtained the PHC Gilibert grant for a 2-year collaboration with the Vilnius University (Lithuania). Our partner is the Department of Bioinformatics, http://www.bti.vu.lt/en/departments/department-of-bioinformatics.