· Older DSM web site
· Pasteur DSM Unit
· UMR 3528 (CNRS)
- Web Servers
· NOMAD-Ref server
· MAP_traject server
· AquaSAXS server
· Job queue status
· Papers by theme
· Papers (List)
· Older papers
· Google Scholar
· Photo du Labo
· DD-NMA (beta)
IntroductionWe are part of the Structural Biology and Chemistry Department in the Institut Pasteur, Paris.
We use experimental techniques such as x-ray crystallography and cryo-EM to visualize at the atomic level the structures and conformational states of
large macromolecules essential to life such as
We complement them with MD simulations, normal modes analysis and Langevin dynamics, in order to go beyond the static
pictures given by these methods and to describe (on a coarse-grained level) the transition path between functional states.
Evolutionary data (sequence alignments) must also be used to uncover what has been conserved throughout evolution
and it usually illuminates the structure.
Structural Molecular Biology relies on three legs, the tripod "Structure-Dynamics-Sequences" or "Architecture-Fluctuations-Evolution",
and all three are necessary for understanding the functional properties of biological macromolecules.
Most optimisation methods that we develop are based on Mean Field theory in statistical physics (see Example).
Our main goal is to design structure-inspired drugs (pharmacology) and re-design active site(s) to make them accept other substrates
(synthetic biology) or simply understand how they work at the molecular level.
NewsPlease note that our web-servers have been disconnected for external use as of April 11th, 2019, for maintenance and updates. They do work, however, internally (on campus). We will go back on-line as soon as possible.
We apologize for any inconvenience this might cause.
Publications by year (2009-2019)
-New structural evidence for an "in trans" base selection mechanism by polymerase mu in Double Strand DNA Repair, with M.R. Lieber's team (USC, CA, USA), accepted in JBC.
-An optimized method to generate large libraries of modified RNAs in Methods.
-Cryo-EM structure of the polD DNA polymerase (DP1+DP2) complex, with or without DNA, in PLoS Biol.
-An updated structure-based classification of all extant DNA polymerases (Here), including polD.
-Fifth DNA Polymerases Meeting in Leiden, NL (Program here).
-CECAM Meeting on Normal Modes in IHP, Paris, September (Program here).
-New and faster calculations of Normal Modes with Patrice Koehl (Ref).
-Design of a polymerase that generates libraries of random RNA in Nucleic Acids Res.
2017-Simulating the transition path between two known conformationss of a macromolecule using mixed ENMs, in J. Chem. Phys. This is a follow up of our previous MAP method (see also P. Koehl in J. Chem. Phys.)
-Organisation with Y.H. Sanejouand of a one day meeting in Normal Mode analysis and Conformational Transitions in Pasteur (30 May 2017)
DNA Polymerases and DNA Repair
-X-ray structure of Archaeal polD DNA polymerase reveals a catalytic site similar to multi-subunit RNA polymerases that are found in all domains of life,
by L. Sauguet, P. Raia, G. Henneke and M. Delarue (Nature Commun).
-Structural basis for an unexpected "in trans" templated activity by TdT: implications for V(D)J recombination and DNA double-strand-breaks repair in eukaryotes,
J. Loc'h, S. Rosario and M. Delarue (Structure).
Pentameric Ligand-gated ion channels (pentaLGICs): drug binding sites in different conformational states
-X-ray structures of GLIC with Xenon, in the open and locally-closed states, with N. Colloc'h (PLoS One).
-TdT structures in complex with a DNA synapsis shed new light on DNA Double-Strand-Break Repair by NHEJ (EMBO J., Mar 2015).
-Structure of a GLIC-GlyR chimera with P.-J. Corringer (PNAS, Feb 2015)
-A structural perspective in the pharmacology of pLGICs (BBA, May 2014)
-Structural basis for ion permeation in GLIC (EMBO Journal, Jan 2013) at 2.4 Angstrom
-Snapshots of Terminal deoxynucleotidyl transferase caught in action: dynamical aspects of the two-metal-ion mechanism (J. Gouge et al., J. Mol. Biol., Jul 2013)
-Structure of Archaeal DNA polymerase (polB) from P. abyssi in editing mode by J. Gouge et al. (JMB)
-A review on cys-loop receptors with P.J. Corringer in Structure
-AquaSAXS software and web site by F. Poitevin (Here).
-High-resolution structure of the extra-cellular domain of GLIC (Here).
-New version of AquaSol software with P. Koehl (Here).
-Structure-function studies of Terminal deoxynucleotidyl transferase (Here).
We offer several applications:
Electrostatics properties of macromolecules can be calculated in an extension of Poisson-Boltzmann theory with free ions and a dipolar solvent model, as developed with P. Koehl (UC Davis) and H. Orland (CEA)
Coarse-grained dynamical properties and Normal Modes using the Elastic Network Model were developed first as a collaboration with Y.H. Sanejouand.
Generating plausible pathways between two known end-points of a structural transition is also a collaboration with H. Orland and P. Koehl.
AquaSAXS, a web-based software to calculate SAXS spectra from PDB coordinates, including the solvent density predicted by AquaSol, is available on-line. See article. The dipolar solvent model used by AqauSAXS is described here. The web server of AquaSol and a new implementation due to P. Koehl is here.
Installation of PDB_Hydro web server (see Ref. here) was done in 2007 with Erik Lindahl and implements the dipolar solvent model in Poisson-Boltzmann electrostatics.
This was later replaced by AquaSol.
Altogether, these sites provide online servers for algorithms such as normal mode calculation.
model refinement, solvation, mutations, homology modeling and transition path calculation.
Go to Older site for more details on the group historical activities.