LAUSR

Protein dynamics are integral to biological function, yet few techniques are sensitive to collective atomic motions. A long-standing goal of X-ray crystallography has been to combine structural information from Bragg diffraction with dynamic information contained in the diffuse scattering background. However, the origin of macromolecular diffuse scattering has been poorly understood, limiting its applicability. We present a finely sampled diffuse scattering map from triclinic lysozyme with unprecedented accuracy and detail, clearly resolving both the inter- and intramolecular correlations. These correlations are studied theoretically using both all-atom molecular dynamics and simple vibrational models. Although lattice dynamics reproduce most of the diffuse pattern, protein internal dynamics, which include hinge-bending motions, are needed to explain the short-ranged correlations revealed by Patterson analysis. These insights lay the groundwork for animating crystal structures with biochemically relevant motions. Protein motion in crystals causes diffuse X-ray scattering, which so far has been very challenging to measure and interpret. Here the authors present a finely sampled diffuse scattering map from triclinic lysozyme, which allows them to resolve inter- and intramolecular correlations and they further analyze the maps using all-atom molecular dynamics simulations and simple vibrational models, revealing the contribution of internal protein motion.