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Introduction

We are part of the Department of Structural Biology and Chemistry in Institut Pasteur, Paris.
Our main field is Structural Molecular Biology and Biophysics, augmented by tools of Computational Biology.

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
- RNA and DNA polymerases involved in genome replication or transactions (repair, transcription, transposition...)
- Ligand-gated ion channels involved in electric nerve signaling and cell-cell communications.

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).

Publications on computational methods by year (2009-2021)

2021

-New article by M. Tekpinar on software to calculate correlations between residues from dynamical or sequence data (Ref).

-New 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.

-New 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 Here.

-See also more on the Optimal Transport theory with P. Koehl and H. Orland: (Ref) and PDF.

2020

-New 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.

2019

-An exploration of multidimensional representation of amino-acids to retrieve structural information from very large sequence alignments (Here).
-See also a recent Review in F1000.

-Coarse-grained dynamics of entire viruses such as the Dengue virus (Ref)

-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.
We are working on applications of this method in the field of structural bioinformatics as well as IA.

2018

-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).

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.)

-New methods in Normal Modes from Elastic Network Models (with Patrice Koehl) for automatic coarse-graining (JCTC) or dazzling speed (Front. Mol. Bios.)

-Organisation with Y.H. Sanejouand of a one day meeting in Normal Mode analysis and Conformational Transitions in Pasteur (30 May 2017)

2016

-Normal Mode analysis of the dynamics of Zika and Dengue virus capsids (Ref)

2015

-Non-local electrostatics made local (Ref)

2014

2013

-Using AquaSol to investigate the stability of microfibrils (Ref)

2012

2011

-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.

2010

-A meeting in I. Pasteur (Paris) was organized in the framework of our France-Stanford exchange Program

-AquaSol full description (Ref)

2009

-The AquaSol model was extended to include solvent-solvent interactions in PRL, see Recomm by F1000.
It goes beyond the Poisson-Boltzmann treatment of macromolecular electrostatics by allowing a variable solvent density, treated as an assembly of dipoles amid free ions and surrounding the charged solute.

Software

The following web sites provide online servers for algorithms such as normal mode calculation, structural refinement, solvation, mutation and (later) transition path calculation.
The primary application is for biological macromolecules like proteins or DNA or complexes thereof.

AquaSAXS, a web-based software to calculate SAXS spectra from PDB coordinates, including the solvent density predicted by AquaSol, see Ref. here.
The underlying dipolar model for the solvent was described in Biophysical Journal (coll. H. Orland).
The web server AquaSol is the newest implementation of this dipolar solvent model, due to P. Koehl.

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.

The NOMAD_Ref web server (see Ref. here) allows to calculate Normal Modes in the Elastic Network Model, and has some applications in X-ray refinement.

The PDB_Hydro web server (see Ref. here) has many features for modeling, in addition to electrostatic calculations (contained in AquaSol).

Go to Older web site for more details on the group activities before 2009.

NOMAD-Ref web server
Normal Mode Analysis
NOMAD-Ref web server
Normal Mode Refinement
PDB_Hydro web server
Mutation & Solvation: Dipolar solvent
PDB_Hydro web server
AquaSaxs web server




  Marc Delarue http://lorentz.dynstr.pasteur.fr