Abstract We have designed and implemented an MD-based pipeline to emulate the entire process of collecting diffraction photos and calculating crystallographic structures of proteins therefrom. Using a structure of lysozyme solved in-house, we constructed a supercell comprised of 125 (5x5x5) crystal unit cells containing a total of 1,000 protein molecules and explicit interstitial solvent. For this system, we recorded two 300-ns MD trajectories at 298 K and 250 K, respectively. A series of snapshots from these trajectories were then used to simulate a fully realistic set of diffraction photographs, which were further fed into the standard pipeline for structure determination. The resulting structures show very good agreement with the underlying MD model not only in terms of coordinates but also B-factors; they are also consistent with the original experimental structure. The developed methodology should find a range of applications, such as optimizing refinement protocols to solve crystal structures and extracting dynamics information from diffraction data or diffuse scattering.