About Us



LATEST NEWS: iGEM Paris team wins first price for Foundational Research at iGEM 2007 Jamboree (November 3-4, MIT, Cambridge MA).

The Laboratoire de Biochimie (BIOC) is a mixed research unit belonging to the École Polytechnique and the Centre National de la Recherche Scientifique (CNRS) in Palaiseau (France). The École Polytechniqueis an excellence center among the top in Europe. In fact, in a recent review by The Times (http://www.thes.co.uk/downloads/rankings/world-rankings-16pages.pdf), it was chosen as the most prestigious academic institution in France, and ranked 6th among all European universities.
The Lab's main research interests are: molecular enzymology and biocatalysis, protein structure and design, biological crystallography and structural bioinformatics. Those topics are treated both experimentally and theoretically. The Laboratory has conducted extensive research on aminoacyl-ARNt synthetases and aminoacid recognition.
After a restructuration in 2003, a Bioinformatics group has been created with two faculty positions (Thomas SIMONSON, Professeur Associe and Alfonso JARAMILLO, Maitre de Conferences), and is still further developing: the size of the group has doubled in the last year. The group is composed of 3 permanent members (2 faculty members and a bioinformatics engineer), 2 postdoc researchers, 4 Ph.D. students and a sabbatical visitor, many of them working on projects in close collaboration with experimental groups.

The Bioinformatics group uses computational protein design techniques to explore aspects of natural evolution that are difficult to address experimentally. Conversely, the mechanisms of natural evolution are exploited to design new proteins with a desired function as thermostability, improved activity to new substrates and tuned specificity. In particular, the team has worked on approaches to study of the influence of protein-protein and protein-ligand interactions on protein evolution. Parallel researches are done using different description levels as proteins on-lattice and off-lattice, and from amino acid level potentials to the atomic description of proteins using molecular mechanics force fields. In all cases the software and algorithms are developed inside the group.

The group has expertise in molecular dynamics simulations and free energy calculations, which have been applied to binding calculations of aaRS (see publications by Prof. SIMONSON). Another research area is computational protein design methodology (see publications by Prof. JARAMILLO) and the double optimization of binding and active sites in the design of enzymes. The group is also working on improved solvation models for ligand-protein interactions in protein design and develops force field parameters from ab initio quantum mechanics calculations for small ligands and its applications to tetracycline-protein interactions.

The group is also developing distributed computing tools through screen savers, using the SETI@HOME paradigm. This project aims to combine scientific results with science popularisation, developing distributed computing protein design Web tools that will coordinate computers of volunteers that donate their idle CPU cycles.

The Bioinformatics group research is funded by the CEA, Programme de Toxicologie Nucléaire (2004-2007) and by the French Ministere de la Recherche, ACI IMPBio, Ëvolution in silico. Evolution de proteines: simulation et controle" (2003-2005).


Latest achievements

The experimental group has a long record of contributions in the field of aminoacyl-ARNt synthetases. Some selected publications are:
  • A. Brevet, J. Chen, S. Commans, C. Lazennec, S. Blanquet, P. Plateau. Anticodon recognition in evolution: switching tRNA specificity of an aminoacyl-tRNA synthetase by site-directed peptide transplantation. J. Biol. Chem. (2003) 278, 30927-30935.
  • T. Crepin, E. Schmitt, Y. Mechulam, P.B. Sampson, M.D. Vaughan, J.F. Honek, S. Blanquet. Use of analogues of methionine and methionyl adenylate to sample conformational changes during catalysis in Escherichia coli methionyl-tRNA synthetase. J. Mol. Biol. (2003) 332, 59-72.
  • S. Commans, M. Lazard, F. Delort, S. Blanquet and P. Plateau. tRNA anticodon recognition and specification within subclass IIb aminoacyl-tRNA synthetases. J. Mol. Biol. (1998) 278, 801-813.
The group has deposited 16 x-ray structures of aaRS in the last 5 years (Prof. MECHULAM et al). The high standard of the group is recognized by its publications (see above), but also by other public distinctions: Prof. BLANQUET is a member of the French Academy of Sciences, founder member of the French Academy of Technology, and directs the interdisciplinary CNRS program "Protéomique et génie des protéines" (France). Prof. SCHMITT has been awarded the bronze medal of the CNRS 2003 for her work on the mechanism of enzyme catalysis using aminoacyl-tRNA synthetases, and on the interaction of enzymes with their ligands using crystallographic methods.

Prof. SIMONSON is an expert in molecular modelling of proteins and their interactions with ligands and other proteins. In the last years he has made important contributions in the field of amino acid recognition by aminoacyl-tRNA synthetases by computer calculations of binding free energies. In the last 10 years, he has directed 6 Ph.D. students and 5 postdoctoral fellows. Selected articles:
  • T. Simon, G. Archontis, and M. Karplus, Free energy simulations come of age: the protein-ligand recognition problem. Acc. Chem. Res. 35 (2002), 430-437.
  • G. Archontis, T. Simonson, M. Karplus. Binding free energies and free energy components from molecular dynamics and Poisson-Boltzmann calculations. Application to amino acid recognition by aspartyl-tRNA synthetase. J. Mol. Biol. 306 (2001), 307-327.
  • G. Archontis, T. Simonson, and M. Karplus. Specific amino acid recognition by aspartyl-tRNA synthetase studied by free energy simulations, J. Mol. Biol. 275 (1998), 823-846.
  • J.G. Arnez, K. Flanagan, D. Moras, and T. Simonson. Engineering an Mg2+ site to replace a structurally conserved arginine in the catalytic center of histidyl-tRNA synthetase by computer experiments. Proteins, 32 (1998), 362-380.
  • A.T. Brunger, P.D. Adams, G.M. Clore, W.L. DeLano, P. Gros, R.W. Grosse-Kunstleve, J.S. Jiang, J. Kuszewski, M. Nilges, N.S. Pannu, R.J. Read, L.M. Rice, T. Simonson, G.L. Warren, 1998, Acta Cryst., D54, 905-921 (more than 5000 citations).

Prof. JARAMILLO is an expert in computational protein design. He is co-author of the protein design software DESIGNER. After a Ph.D. on theoretical physics he moved to biology and he had postdoctoral positions with Prof. Wodak (U. Toronto) and Prof. Karplus (first at the Univ. Luis Pasteur, Strasbourg, and later at Harvard U., USA). After 4 years of postdoctoral work he joined the faculty of the Department of Biology at the Ecole Polytechnique. He continues to collaborate with Prof. Wodak and Prof. Karplus, and also with the group of Prof. Hilvert (ETH, Zurich). He has supervised two master thesis in protein design and is currently supervising the postdoctoral research of Dr. TORTOSA. Relevant publications of Prof. JARAMILLO:
  • A. Jaramillo and S.J. Wodak. Computational Protein Design Is a Challenge for Implicit Solvation Models. Biophys J. 88 (2005), 156-171.
  • K. Ogata, A. Jaramillo, W. Cohen, J. Briand, F. Connan and S.J. Wodak. Automatic Sequence Design of MHC Class-I Binding Peptides Impairing CD8+T Cell Recognition. J. Biol. Chem. 278 (2003), 1281-1290.
  • A. Jaramillo, L. Wernisch, S. Hery and S.J. Wodak. Folding free energy function selects native-like protein sequences in the core but not on the surface. Proc. Natl. Acad. Sci. 99 (2002), 13554-13559.
  • A. Jaramillo, S.J. Wodak, L. Wernisch and S. Hery. Automatic procedures for protein design. Combinatorial Chemistry and High Throughput Screening 4, 639-655 (2001).
Finally, it should be noted that of the students and postdocs (many of them of a nationality other than French) who have been trained in the group, the last two have obtained a tenure track and a permanent position respectively. The group is in fact paying attention to offering best chances to young people for their future career.

(c) Alfonso Jaramillo.
Last modified on 16 November 2007.