Molecular modeling of small, medium-sized proteins to large complex systems

http://thcgerm.free.fr/spip.php?article123National audienceStructural biology studies provide key insights for life sciences, ranging from drug discovery to biofuel engineering, and from understanding metabolic disease mechanisms to improve human and animal health. Nuclear Magnetic Resonance (NMR) spectroscopy enables high-resolution three-dimensional studies of biomolecules and provides unique information on molecular dynamics and interactions. The downside of protein structure determination by NMR is however the elaborated data analysis workflow, involving many imperfect experimental and computational steps. In fact, NMR-only driven structure determination projects will always be limited by the intrinsic experimental imperfection of the technique, therefore truly robust, objective and highly accurate data analysis of large protein complexes (> 30kDa) is hard to achieve using NMR data only.The current limitations of NMR studies can however be bridged by simultaneous consideration of multiple types of information. A promising strategy consists in supplementing the conventional structure determination process with a prior knowledge extracted from databases. Here we will describe such an integrated, hybrid approach for NMR structure elucidation. We will present application examples for rapid and accurate structure determination of small to medium-sized soluble proteins and the de novo structure of a 28kDa protein dimer in a 2.5MDa viral capsid assembly by solid-state NMR