Structural Bioinformatics  

  HEADProf. NILGES Michael /
  MEMBERSDr. BLONDEL Arnaud / Dr. CHAU Pak-Lee / DUCLERT_SAVATIER Nathalie / Dr. HUYNH Tru / Dr. MALLIAVIN Thérèse / Dr. STOVEN Véronique / Dr. YERAMIAN Edouard / Dr. MARKWICK Phineus / Dr. MARTINEZ Leandro / GIGANTI David / BARDIAUX Benjamin / BERNARD Aymeric / PERIN Olivier / LAINE Elodie / BASTIANELLI Giaccomo / COLAS Claire

  Annual Report

The aim of our research is to complement structural studies (X-rays, NMR, Electron microscopy) with in silico studies, to:

• better determine and predict three-dimensional structures;

• better understand molecular recognition and molecular interactions.

Our research topics include medically relevant molecular processes (infectious diseases, cancer, and the action of general anesthetics). Collaboration with experimental groups on campus, and our own experimental projects, are of fundamental importance for the group.

New strategies for the structural analysis of NMR data developed in the group make experimental structure determination more reliable, and allow to obtain an unbiased estimate of quality of an NMR structure. Other developments include new probabilistic methods for sequence alignment RNA structure prediction, and gene prediction by physics based genome analysis.

Studies on the dynamics of protein-protein interactions by docking and molecular dynamics calculations have provided new insights into the interplay between protein flexibility and molecular recognition, and the thermodynamics of protein-ligand interactions. The prediction of conformational changes during the binding of two proteins, or a protein and a small ligand, remains an important aim.

The field of protein-ligand interactions has fundamental as well as more applied aspects. In several collaborations with experimental groups we use empirical strategies for ligand docking and virtual screening. Targets include proteins from P. falciparum, T. brucei, T. cruzi, M. tuberculosis and B. anthracis. We have identified inhibitors for proteins from P. falciparum, M. tuberculosis, T. cruzi and B. anthracis that were validated experimentally.

The work on general anesthetics includes two axes: the study of the GABA_A receptor using structure prediction and computer simulations, to elucidate its mechanism of action; and the study of the interaction of general anesthetics and membranes. Our previous work has suggested a mechanism for the pressure-induced reversal of general anesthetic action, and we are now verifying this mechanism using neutron scattering experiments and free-energy change calculations.

Keywords: Structural Bioinformatics, Molecular Dynamics, Genome Analysis, Gene Prediction, Structure Prediction, Protein-Protein Interactions, NMR data analysis


Figure 1: Illustration of an important part of the activity of the unit. Starting from structural information for a protein, we use various methods to predict and characterize its interactions with other molecules. The results serve as input for further experimental studies.


Rieping, W; Habeck, M; Nilges, M. 2005. Inferential structure determination. SCIENCE 309 (5732): 303-306

Grunberg, R; Nilges, M; Leckner, J. 2006. Flexibility and conformational entropy in protein-protein binding. STRUCTURE 14 (4): 683-693

Chau, PL; Hoang, PNM; Picaud, S; Jedlovszky, P. 2007. A possible mechanism for pressure reversal of general anaesthetics from molecular simulations. CHEMICAL PHYSICS LETTERS 438 (4-6): 294-297.

Yeramian, E; Debonneuil, E. 2007. Probabilistic sequence alignments: Realistic models with efficient algorithms. PHYSICAL REVIEW LETTERS 98 (7): art. no.-078101.

Laine, E; Yoneda, JD; Blondel, A; Malliavin, T. 2008. The conformational plasticity of calmodulin upon calcium complexation gives a model of its interaction with the oedema factor of Bacillus anthracis. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 71 (4): 1813-1829.

Activity Reports 2009 - Institut Pasteur
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