High pressure (HP) is a unique parameter to explore the complex free energy landscape of macromolecules, from the native folded state with the lowest Gibbs free energy to the completely unfolded states. In solution, protein molecules fluctuate between various conformers with different populations. According to Le Chatelier’s principle, pressure favours phases with smaller specific volume and increases populations of the more compact, higher-energy conformers, which may become the dominant species in the solution at the expense of the native state. These higher energy conformers are often of high biological relevance (close identity with intermediate/transition states during the course of functional mechanism, or with intermediate states during unfolding). Such evolution of populations under HP has been observed by NMR on several proteins. It can also occur in the crystalline state.
The perturbation of a biomolecular system by pressure has many other applications, for instance the study of the molecular basis of adaptation of life to extreme conditions, protein aggregation producing amyloid fibers, dissociation of oligomeric proteins, mechanisms of folding and unfolding. For these various reasons, recent years have witnessed a growing interest in introducing pressure as a variable acting on biosystems. Many methods routinely used at atmospheric pressure for studies of structure and kinetics of macromolecules have been adapted to HP. Hydrostatic pressure is a very efficient parameter for inducing conformational changes in solution as compared to concentration, temperature and denaturants. High profile time-resolved work has been done recently on protein folding and structural transformations in lipid membranes.
The instrumental palet includes two complementary high resolution structural methods, NMR and x-ray crystallography (HPMX). HPMX using synchrotron radiation (SR) is now a full-fledged technique, which has been applied to a variety of proteins, virus and nucleic acid components. Another important SR-based technique is small-angle X-ray scattering. Circular dichroism and X-ray absorption spectroscopy would clearly benefit from HP environment, but still require instrumental developments. V/UV and IR methods (fluorescence methods, Raman, IR spectro-microscopy) are well developed using laboratory and SR sources. Most neutron-based techniques have also been adapted to HP environment.
It is timely to organize an international conference in order to extend applications of HP in molecular biophysics to the broader French and international community. The conference will cover an overview of fundamental interest of HP for molecular biophysics, instrumentation, applications and results concerning the main techniques coupled with HP (based or not on SR). The coupling of experimental results with simulations is another important part of the programme, with a dedicated session and a half-day satellite workshop.