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We are part of the Department of Structural Biology and Chemistry in Institut Pasteur, Paris.
We use experimental techniques such as crystallography and cryo-electron microscopy to visualize at the atomic level the structure of molecules essential to life and to understand their functional properties, especially for
We complement them with computational approaches such as molecular dynamics (atomic models), normal modes dynamics (coarse-grained models) and statistical thermodynamics, in order to go beyond the essentially static pictures given by these methods.
Computational tools allow to make use of the important information contained in massive sequence data of related molecules in the tree of life and help to understand what is essential in their active site structure and how it is modulated.
When possible we study their structure in the context of their partners in larger macromolecular complexes and try to dissect the molecular interactions between them
in order to understand possible emerging collective properties (systems biology).
Our main goal is to understand how these molecular machines work at the atomic level so as to design structure-inspired drugs (pharmacology and drug discovery) and re-design their active site(s) to make them accept other substrates (synthetic biology).
N.B. Due to some security issues in our servers, most of our web services are not available outside campus.
Marc Delarue elected to Academia Europaea in 2021
For Polymerases only, see Here
For Ion channels only, see Here
For Methods only, see Here
Publications by year (2009-2021)
-Structural dynamics and determinants of 2-aminoadenine specificity in DNA polymerase DpoZ of vibriophage ϕVC8.
-Extracting Dynamical Correlations and Identifying Key Residues for Allosteric Communication in Proteins by correlationplus.
-An article by Dariusz Czernecki et al. in Nature Commun.
-As a follow-up of this article, we show that only 3 genes of this phage are necessary to incorporate the new base in a bacterial genome, at least partially BioRxiv. This work is now published in Nature Commun. Here.
-An article by Clement Madru et al. on a new and very efficient way to express and purify in E. coli the different subunits constituting the RNA polymerase of SARS2-Covid19 in PLoS One Here.
-An article with P. Koehl and H. Orland in J. Phys. Chem. B on an application of the extended dipolar Poisson-Boltzmann formalism to detect simultaneously
druggable pockets in proteins, including those with a hydrophobic character Here.
-An article with P. Koehl and H. Orland in J. Comput. Chem. on the parametrization of Elastic Networks for best Normal Modes Analysis of Large biological Macromolecules
-Structures of both open and closed forms by Haidai Hu of a new bacterial pLGIC related to ELIC and sensitive to Ca++ depletion,
with two additional N-terminal domains and an unusual allosteric regulation at the supramolecular level
(Ref and PDF).
-An article in Acta Cryst D by Z. Fourati et al. on molecules binding to the vestibular allosteric binding site in pLGICs (GLIC)
-An article in Phys. Rev. E with P. Koehl and H. Orland on the solution of the unbalanced Optimal Transport Problem with statistical physics methods Here.
-An article in Biomolecules by C. Samson et al. on the structures of key intermediates in the reaction of a DNA polymerase evolved to accept xeno-nucleotides and its substrates
-An article in Nature Commun. by C. Madru et al. on the cryo-EM structure of archaeal DNA polymerase polD + DNA + PCNA (Here).
-A structural model for the interaction of human Pol mu with an NHEJ junction containing a DNA double-strand-break, published in JBC, see .
This is a collaboration with the group of M.R. Lieber (USA).
-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).
-With main authors Patrice Koehl (UC Davis) and Henri Orland (CEA, Saclay), a new look at
Optimal Transport theory using the tools of statistical mechanics, just published in Physical Review Letters
(PRL) and Phys Rev E (PRE).
See articles here, PRL.pdf and PRE.pdf.
-Co-organization of a CECAM Meeting on Normal Modes in IHP, Paris, September (Program here).
-New and faster calculations of Normal Modes with Patrice Koehl (Ref).
-Talk at the Fifth DNA Polymerases Meeting in Leiden, NL (Program here).
-Design of a polymerase that generates libraries of random RNA polymers 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).
See Recomm by F1000.
-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, by
J. Loc'h, S. Rosario and M. Delarue (Structure).
See Recomm by F1000.
Pentameric Ligand-gated ion channels (pentaLGICs): drug binding sites in different conformational states
-X-ray structures of GLIC bound to Xenon, in the open and locally-closed states, with N. Colloc'h (PLoS One).
-X-ray structures of GLIC bound to Bromoform, supplemented by Molecular Dynamics studies by M. Baaden and coll. (Structure).
-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 functional GLIC-GlyR chimera with P.-J. Corringer (PNAS, Feb 2015)
-Structural basis for the gating mechanism in GLIC (PNAS, Jan 2014), see Recomm by F1000
-A structural perspective in the pharmacology of pLGICs - a review (BBA, May 2014)
-Snapshots of TdT caught in action: dynamical aspects of the two-metal-ion mechanism by J. Gouge et al. (J. Mol. Biol., Jul 2013)
-Structural basis for ion permeation in GLIC (EMBO Journal, Jan 2013) at 2.4 Angstrom
-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
-Atomic structure of a complex of general anesthetics with GLIC is published in Nature in 2011, Recommended by F1000
-A web site and software to analyze SAXS data and fit them to molecular models by Fred Poitevin et al. in NAR web site issue.
-A meeting in I. Pasteur (Paris) was organized in the framework of our France-Stanford exchange Program
-Atomic structure of the extra-cellular (water-soluble) domain of pentameric ligand-gated ion-channel at high resolution in J. Mol. Biol.
-Extensive mutational analysis of TdT and different ways to transform it into a template-directed DNA polymerase by F. Romain et al. in Nucleic Acids Research NAR
-The AquaSol model was extended to include solvent-solvent interactions in PRL, see Recomm by F1000.
The following web sites provide online servers for algorithms such as normal mode
calculation, structural refinement, solvation, mutation and (later) transition path calculation.
a web-based software to calculate SAXS spectra from PDB coordinates,
including the solvent density predicted by AquaSol, see Ref. here.
MinActionPath (MAP) web server can be used to generate the most probable trajectory between two known structural forms
of the same macromolecule (see Ref. here).
The algorithm was greatly accelerated by P. Koehl, as described here.
Go to Older web site for more details on the group activities before 2009.