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)

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:

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