Advances in high-pressure biophysics: status and prospects of macromolecular crystallography.

A survey of the main interests of high pressure for molecular biophysics highlights the possibility of exploring the whole conformational space using pressure perturbation. A better understanding of fundamental mechanisms responsible for the effects of high pressure on biomolecules requires high-resolution molecular information. Thanks to recent instrumental and methodological progress taking advantage of the remarkable adaptation of the crystalline state to hydrostatic compression, pressure-perturbed macromolecular crystallography is now a full-fledged technique applicable to a variety of systems, including large assemblies. This versatility is illustrated by selected applications, including DNA fragments, a tetrameric protein, and a viral capsid. Binding of compressed noble gases to proteins is commonly used to solve the phase problem, but standard macromolecular crystallography would also benefit from the transfer of experimental procedures developed for high-pressure studies. Dedicated short-wavelength synchrotron radiation beamlines are unarguably required to fully exploit the various facets of high-pressure macromolecular crystallography.