Seminars – Protein flexibility through in silico approaches

EVENT : C3BI Seminars

Protein flexibility through in silico approaches

Main speaker : Alexandre de Brevern, from Permanent Researcher INSERM – Dynamics of Structures and Interactions of Macromolecules in Biology – University Paris Diderot Date : 06/04/2017 at 02:00 pm Location : Auditorium Francois Jacob – BIME (26) ,Institut Pasteur, Paris

Protein flexibility through in silico approaches

The function of a protein is directly dependent on its 3-dimensional structure. Visualization tools have oversimplified our views of protein structures. Often, they are considered as macromolecules with repetitive structures as rigid while the connecting loops as flexible or even disordered. in silico approaches are interesting tools to tackle this critical question of protein flexibility. Moreover, it allows applying other criteria than B-factors, to define flexibility [1].
We have previously developed different structural alphabets (SAs) [2], [3]. They are libraries of small protein fragments that are able to approximate every part of protein structures, making them more precise than classical secondary structures.
During this talk, I will present:
* How a more precise and complete description of protein backbone conformation can be obtained using SAs for the structural analysis? With examples from definition of ligand binding sites to superimposition of protein structures [4].
* How SAs are also well suited to perform prediction of protein flexibility from the sequence [5]?
* How have we also used them to analyse the dynamics of protein structures in a case of a transmembrane protein [6]
* For integrins implicated in pathologies [7], [8].
* Finally, I will present unpublished results based on a selected a representative set of Molecular Dynamic (MD) performed on 169 protein structures. We show how the SAs can underline specific change of local protein conformations during dynamics [9], especially using PBxplore tool [10].

1. Craveur, P., Joseph, A.P., Esque, J., Narwani, T.J., Noël, F., Shinada, N., Goguet, M., Leonard, S., Poulain, P., Bertrand, O., Faure, G., Rebehmed, J., Ghozlane, A., Swapna, L.S., Bhaskara, R.M., Barnoud, J., Télétchéa, S., Jallu, V., Cerny, J., Schneider, B., Etchebest, C., Srinivasan, N., Gelly, J.-C., de Brevern A.G.: Protein flexibility in the light of structural alphabets., Frontiers in Molecular Biosciences – Structural Biology, 2:20. (2015)
2. de Brevern, A.G. , Etchebest, C., Hazout, S.: Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks, Proteins, 41:271-287. (2000)
3. Bornot, A., Etchebest, C., de Brevern, A.G. : A new prediction strategy for long local protein structures using an original description, Proteins, 76:570-87. (2009)
4. Joseph, A.P., Agarwal, G., Mahajan, S., Gelly, J.-C., Swapna, L.S., Offmann, B., Cadet, F., Bornot, A., Tyagi M., Valadié, H., Schneider, B., Etchebest, C., Srinivasan, N., de, Brevern, A.G. : A short survey on Protein Blocks, Biophysical Reviews, 2:137-145. (2010)
5. de Brevern, A.G., Bornot, A., Craveur, P., Etchebest, C., Gelly, J.-C. : PredyFlexy: Flexibility and Local Structure prediction from sequence, Nucleic Acid Res, 40:W317-22. (2012)
6. de Brevern, A.G., Wong, H., Tournamille, C., Cartron, J.-P., Colin, Y., Le Van Kim, C., Etchebest, C. : A structural model of seven transmembrane helices receptor, Duffy Antigen / Receptor for Chemokines (DARC), Biochem Biophys Acta, 1724:288-306. (2005)
7. Jallu, V., Poulain, P., Fuchs, P.F., Kaplan, C., de Brevern, A.G.: Modeling and Molecular Dynamics of HPA-1a and -1b Polymorphisms: Effects on the Structure of the β3 Subunit of the αIIb/β3 Integrin, Plos One, 7:e47304. (2010)
8. Jallu, V., Poulain, P., Fuchs, P.F., Kaplan, C., de Brevern, A.G.: Modeling and molecular dynamics simulations of the V33 variant of the integrin subunit β3: structural comparison with the L33 (HPA-1a) and P33 (HPA-1b) variants, Biochimie, 105:84-90. (2014)
9. Narwani, T., Craveur, P., Shinada, N., Santuz, H., Rebehmed, J., Etchebest, C., de Brevern, A.G. Dynamics and deformability of α-, 310- and π-helices, submitted.
10.Barnoud, J., Santuz, H., Craveur, P., Joseph, A.P., Jallu, V., de Brevern, A.G., Poulain, P. PBxplore: a tool to analyze local protein 
structure and deformability with Protein 
Blocks,, in preparation.

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