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IntroductionWe use classical 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
-DNA polymerases involved in DNA replication or DNA Repair
-ligand-gated ion channels involved in cell-cell communications.
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 try 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.
We believe Structural Molecular Biology relies on three legs, the tripod "Structure-Dynamics-Sequences" or "Architecture-Fluctuations-Evolution"
to lead to a proper understanding of the functional properties of biological macromolecules.
Our main goal is to design structure-inspired drugs (pharmacology) and re-design active site(s) to make them accept other substrates (synthetic biology).
NewsPlease note that our web-servers have been disconnected for external use as of April 11th, 2109, for maintenance and updates.
We will go back on-line as soon as possible.
We apologize for any inconvenience this might cause.
Publications by year (2009-2019)
-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 forms 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).
-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)
We offer several applications:
Electrostatics with free ions and a dipolar solvent model with P. Koehl (UC Davis) and
H. Orland (CEA)
a web-based software to calculate SAXS spectra from PDB coordinates,
including the solvent density predicted by AquaSol, is now available on-line.
Installation of PDB_Hydro web server (see Ref. here) was done in 2007 and implements the dipolar solvent model in Poisson-Boltzmann electrostatics.
Altogether, these sites provide online servers for algorithms such as normal mode calculation.
refinement, solvation, mutation and (later) transition path calculation.
Go to Older site for more details on the group activities.