over different molecular configurations[@Maia2009] lowers the speckle contrast relative to the mean scattering intensity within each resolution shell. We expect radiation damage to cause a similar loss of contrast. Not only is the amplitude of the speckle structure reduced, but speckle structure also fluctuates from shot-to-shot due to damage, in addition to the fluctuations due to changing orientation and shot-noise. We will use the term “damage noise" to refer to these fluctuations of speckle structure due to damage. So far damage noise has not been considered in studies of 3D dataset assembly. Here we present calculations of damage noise per diffraction pattern due to spatially uncorrelated damage processes, which include ionization and ion diffusion but not the Coulomb explosion of the molecule. An analysis of damage noise as a function of pulse duration reveals a gating effect in single molecule diffraction, whereby long pulses measure an equivalent amount of information about the average structure to shorter pulses of the same intensity. Theoretical predictions of damage noise are also the first step to understanding how orientation determination and 3D data assembly can be performed with data affected by radiation damage.

An alternative to alignment via post-processing is to experimentally align isolated 