bioRxiv2017
SynopsisA molecular dynamics simulation of diffuse X-ray scattering from staphylococcal nuclease crystals is greatly improved when the unit cell model is expanded to a 2x2x2 layout of eight unit cells. The dynamics are dominated by internal protein motions rather than rigid packing interactions.\n\nAbstractMolecular dynamics (MD) simulations of Bragg and diffuse X-ray scattering provide a means of obtaining experimentally validated models of protein conformational ensembles. This paper shows that, compared to a single periodic unit cell model, the accuracy in simulating diffuse scattering is increased when the crystal is modeled as a periodic supercell, consisting of a 2x2x2 layout of eight unit cells. The MD simulations capture the general dependence of correlations on the separation of atoms. There is substantial agreement between the simulated Bragg reflections and the crystal structure; there are local deviations, however, indicating both the limitation of using a single structure to model disordered regions of the protein and local deviations of the average structure away from the crystal structure. Although it was anticipated that a longer duration simulation might be required to achieve convergence of the diffuse scattering calculation using the supercell model, only a microsecond is required, the same as for the unit cell. Rigid protein motions only account for a small fraction of the variation in atom positions from the simulation. The results indicate that protein crystal dynamics can be dominated by internal motions rather than packing interactions, and that MD simulations can be combined with Bragg and diffuse X-ray scattering to model the protein conformational ensemble.