Anisotropic time-resolved solution X-ray scattering patterns from explicit-solvent molecular dynamics.

Time-resolved wide-angle X-ray scattering (TR-WAXS) is an emerging experimental technique used to track chemical reactions and conformational transitions of proteins in real time. Thanks to increased time resolution of the method, anisotropic TR-WAXS patterns were recently reported, which contain more structural information than isotropic patterns. So far, however, no method has been available to compute anisotropic WAXS patterns of biomolecules, thus limiting the structural interpretation. Here, we present a method to compute anisotropic TR-WAXS patterns from molecular dynamics simulations. The calculations accurately account for scattering of the hydration layer and for thermal fluctuations. For many photo-excitable proteins, given a low intensity of the excitation laser, the anisotropic pattern is described by two independent components: (i) an isotropic component, corresponding to common isotropic WAXS experiments and (ii) an anisotropic component depending on the orientation of the excitation dipole of the solute. We present a set of relations for the calculation of these two components from experimental scattering patterns. Notably, the isotropic component is not obtained by a uniform azimuthal average on the detector. The calculations are illustrated and validated by computing anisotropic WAXS patterns of a spheroidal protein model and of photoactive yellow protein. Effects due to saturated excitation at high intensities of the excitation laser are discussed, including opportunities to extract additional structural information by modulating the laser intensity.