Dealing with structural variability in molecular replacement and crystallographic refinement through normal-mode analysis
Résumé
Normal-mode analysis (NMA) can be used to generate multiple structural variants of a given template model, thereby increasing the chance of finding the molecular-replacement solution. Here, it is shown that it is also possible to directly refine the amplitudes of the normal modes against experimental data (X-ray or cryo-EM), generalizing rigid-body refinement methods by adding just a few additional degrees of freedom that sample collective and large-amplitude movements. It is also argued that the situation where several (conformations of) models are present simultaneously in the crystal can be studied with adjustable occupancies using techniques derived from statistical thermodynamics and already used in molecular modelling.