New paper: Understanding small biomolecule-biomaterial interactions: A review of fundamental theoretical and experimental approaches for biomolecule interactions with inorganic surfaces

Interactions between biomolecules and inorganic surfaces play an important role in natural environments and in industry, including a wide variety of conditions: marine environment, ship hulls (fouling), water treatment, heat exchange, membrane separation, soils, mineral particles at the earth's surface, hospitals (hygiene), art and buildings (degradation and biocorrosion), paper industry (fouling) and more. To better control the first steps leading to adsorption of a biomolecule on an inorganic surface, it is mandatory to understand the adsorption mechanisms of biomolecules of several sizes at the atomic scale, that is, the nature of the chemical interaction between the biomolecule and the surface and the resulting biomolecule conformations once adsorbed at the surface. This remains a challenging and unsolved problem. Here, we review the state of art in experimental and theoretical approaches. We focus on metallic biomaterial surfaces such as TiO(2) and stainless steel, mentioning some remarkable results on hydroxyapatite. Experimental techniques include atomic force microscopy, surface plasmon resonance, quartz crystal microbalance, X-ray photoelectron spectroscopy, fluorescence microscopy, polarization modulation infrared reflection absorption spectroscopy, sum frequency generation and time of flight secondary ion mass spectroscopy. Theoretical models range from detailed quantum mechanical representations to classical forcefield-based approaches.

Dominique Costa, Pierre-Alain Garrain, and Marc Baaden in J Biomed Mater Res A. ASAP (27 Sep 2012)

New paper: Modeling complex biological systems: From solution chemistry to membranes and channels

Complex biological systems are intimately linked to their environment, a very crowded and equally complex solution compartmentalized by fluid membranes. Modeling such systems remains challenging and requires a suitable representation of these solutions and their interfaces. Here, we focus on particle-based modeling at an atomistic level using molecular dynamics (MD) simulations. As an example, we discuss important steps in mod- eling the solution chemistry of an ion channel of the ligand-gated ion channel receptor fam- ily, a major target of many drugs including anesthetics and addiction treatments. The bacte- rial pentameric ligand-gated ion channel (pLGIC) called GLIC provides clues about the functional importance of solvation, in particular for mechanisms such as permeation and gat- ing. We present some current challenges along with promising novel modeling approaches.

Benoist Laurent, Samuel Murail, Franck Da Silva, Pierre-Jean Corringer, and Marc Baaden in Pure and Applied Chemistry ASAP

New paper: Mixing atomistic and coarse grain solvation models for MD simulations: let WT4 handle the bulk.

Accurate simulation of biomolecular systems requires the consideration of solvation effects. The arrangement and dynamics of water close to a solute is strongly influenced by the solute itself. However, as the solute-solvent distance increases, the water properties tend to those of the bulk liquid. This suggests that bulk regions can be treated at a coarse grained (CG) level, while keeping the atomistic details around the solute. Since water represents about 80% of any biological system, this approach may offer a significant reduction in the computational cost of simulations without compromising atomistic details. We show here that mixing the popular SPC water model with a CG model for solvation (called WatFour) can effectively mimic the hydration, structure and dynamics of molecular systems composed of pure water, simple electrolyte solutions and solvated macromolecules. As a non trivial example, we present simulations of the SNARE membrane fusion complex, a trimeric protein-protein complex embedded in a double phospholipid bilayer. Comparison with a fully atomistic reference simulation illustrates the equivalence between both approaches.

Leonardo Darre, Alex Tek, Marc Baaden, and Sergio Pantano in J. Chem. Theory Comput., Just Accepted Manuscript
DOI: 10.1021/ct3001816 - Publication Date (Web): June 4, 2012 -

New paper: A locally closed conformation of a bacterial pentameric proton-gated ion channel

Pentameric ligand-gated ion channels mediate signal transduction through conformational transitions between closed-pore and open-pore states. To stabilize a closed conformation of GLIC, a bacterial proton-gated homolog from Gloeobacter violaceus whose open structure is known, we separately generated either four cross-links or two single mutations. We found all six mutants to be in the same 'locally closed' conformation using X-ray crystallography, sharing most of the features of the open form but showing a locally closed pore as a result of a concerted bending of all of its M2 helices. The mutants adopt several variant conformations of the M2-M3 loop, and in all cases an interacting lipid that is observed in the open form disappears. A single cross-linked mutant is functional, according to electrophysiology, and the locally closed structure of this mutant indicates that it has an increased flexibility. Further cross-linking, accessibility and molecular dynamics data suggest that the locally closed form is a functionally relevant conformation that occurs during allosteric gating transitions.

By Marie S Prevost, Ludovic Sauguet, Hugues Nury, Catherine Van Renterghem, Christèle Huon, Frederic Poitevin, Marc Baaden, Marc Delarue & Pierre-Jean Corringer

Postdoc or engineer position now open within the ExaViz project

We are seeking a highly motivated candidate to design and implement a next generation visualization platform for analysis of large-scale molecular simulations. In particular, we target two grand challenge applications: modeling a complete influenza virus and analyzing extensive simulations of the GLIC receptor that we recently published in Nature and PNAS, two leading journals. Project foundations were previously established, providing a well defined framework to get started (FvNano). Using visual analytics approaches and high performance interactive graphics, you will implement readily usable state-of-art tools scaling up to the next generation of simulations. This position is a unique training opportunity in a multi-disciplinary environment in collaboration with four leading teams in France and two international partners in the U.K. and in Germany.

PDF-page of this job offer and general background:

FvNano ends, ExaViz begins..

The FvNano project officially ended on 31 december 2011. We are currently updating the webpages because the project still produces output in the form of publications, posters, websites and code that can be downloaded and tested. Have a look at the FvNano webpage for the latest details.
FVNano-related research will continue in the ExaViz project about exa-scalable visual analysis for life & materials sciences. ExaViz already has its own website with a job section and several offers. An overall description of the project and the teams involved is also provided.

New paper out: Enzyme Closure and Nucleotide Binding Structurally Lock Guanylate Kinase

We investigate the conformational dynamics and mechanical properties of guanylate kinase (GK) using a multiscale approach combining high-resolution atomistic molecular dynamics and low-resolution Brownian dynamics simulations. The GK enzyme is subject to large conformational changes, leading from an open to a closed form, which are further influenced by the presence of nucleotides. As suggested by recent work on simple coarse-grained models of apo-GK, we primarily focus on GK's closure mechanism with the aim to establish a detailed picture of the hierarchy and chronology of structural events essential for the enzymatic reaction. We have investigated open-versus-closed, apo-versus-holo, and substrate-versus-product-loaded forms of the GK enzyme. Bound ligands significantly modulate the mechanical and dynamical properties of GK and rigidity profiles of open and closed states hint at functionally important differences. Our data emphasizes the role of magnesium, highlights a water channel permitting active site hydration, and reveals a structural lock that stabilizes the closed form of the enzyme.
By Olivier Delalande, Sophie Sacquin-Mora and Marc Baaden, published in Biophysical Journal Volume 101, Issue 6, 1440-1449, 21 September 2011.

Visualization: teaching resources added

I have added two talks on visualization to the teaching resources.
  1. The first document explains some of the background related to molecular visualization on GPUs. It relates to a talk given at "Journée visu 2010" on 5-Oct-2010 at EDF Clamart: Visualizing Molecules on GPUs talk (PDF). You can also find related example code and extensive discussion at the HyperBalls website. A second, more detailed document is available, with some bits in French, some in English.
  2. Ce document "La chimie fait son cinéma en visualisation moléculaire" explique quelques fondements de la visualisation sur cartes graphiques (GPU). Cette conférence a été présentée en mai 2011 aux MIEC-JIREC 2011. Vous pouvez télécharger le document ici: La chimie fait son cinéma en visualisation moléculaire (PDF, French+English).

HyperBalls representation: publication and website now online!

The article "GPU-accelerated atom and dynamic bond visualization using hyperballs: A unified algorithm for balls, sticks, and hyperboloids" is now online at the Journal of Computational Chemistry website (see abstract below). There is a dedicated website about all things HyperBall, comprising some background information, a picture and movie gallery and download links: more...

Visualization: Animation of electrostatic field lines

The visualization of field lines of the membrane-inserted BLT2 GPCR is implemented as WebGL-page using SpiderGL. There is an animation at my Youtube channel, a video that can be downloaded and a web-browser capable page at This visualization is supplementary material to the article Electrostatically-driven fast association and perdeuteration allow transferred cross-relaxation detection for G protein-coupled receptor ligands with equilibrium dissociation constants in the high-to-low nanomolar range by Catoire et al., Journal of Biomolecular NMR 2011.

Such molecular visualization applications of SpiderGL are described in more detail in M. Callieri et al., Visualization methods for molecular studies on the web platform, The Web3D 2010 Conference, 22-24 July 2010, Los Angeles, California

An enhanced electronic table about GPU-powered molecular visualization tools

In our paper "GPU-powered tools boost molecular visualization" we have an overview table with molecular visualization tools and methods that benefit from current GPU technology. You can now access an enhanced electronic version of this table with illustrations, software download links and videos to watch describing the methods. Check it out at

New paper out: X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel

General anaesthetics have enjoyed long and widespread use but their molecular mechanism of action remains poorly understood. There is good evidence that their principal targets are pentameric ligand-gated ion channels1, 2 (pLGICs) such as inhibitory GABAA (γ-aminobutyric acid) receptors and excitatory nicotinic acetylcholine receptors, which are respectively potentiated and inhibited by general anaesthetics. The bacterial homologue from Gloeobacter violaceus3 (GLIC), whose X-ray structure was recently solved4, 5, is also sensitive to clinical concentrations of general anaesthetics6. Here we describe the crystal structures of the complexes propofol/GLIC and desflurane/GLIC.Read more...

Joyeux Noël / Merry X-mas & DNase

Nos travaux sur la DNase I ont servi pour les voeux de l'IDRIS 2011. La carte animée en Flash est accessible sur ce site. Le message accompagnant la carte était "Le personnel de l'IDRIS vous présente ses meilleurs voeux pour la nouvelle année 2011".
Our work on the DNase I enzyme was featured in the IDRIS supercomputer center's 2011 season's greetings. The animated card is accessible from this site. The message going with it was "IDRIS team wishes you a happy new year 2011".

Predoctoral opening in the Molecular and Cellular Modeling group at Heidelberg Institute for Theoretical Studies

Predoctoral scholarship in the Molecular and Cellular Modeling group at the Heidelberg Institute for Theoretical Studies (HITS) in Heidelberg, Germany with Prof. Wade.
We are seeking a highly motivated scientist to join the Molecular and Cellular Modeling group at HITS for their doctoral studies. The research project will involve computational modelling and simulation of protein interactions.

News blog opens! Let's start with a job announcement!

Hi, I decided to add a blog-like news section to the site and will try to update frequently. Let's start with something useful, a job announcement. My colleague Fabio Sterpone has the following position to fillRead more...