Small-angle X-ray scattering profile calculation for high-resolution models of biomacromolecules

We introduce a new approach to calculating small-angle X-ray scattering (SAXS) profiles from high-resolution atomic structures, which is realized in the open-source software <i>AUSAXS</i>. We employ an efficient implementation of the Debye equation, incorporating both accurate excluded volume models and a novel hydration shell model based on explicit dummy atoms. Two new excluded volume models are presented: (i) a simple, heterogeneous equivalent atom model, and (ii) a grid-based model. The two approaches reduce the risk of overfitting by either eliminating fitting parameters or introducing a safer volume scaling method. These models are compared with the traditional Gaussian sphere method, which is widely used in existing software. The comparisons reveal significant shortcomings in previously accepted methods, suggesting they may be more prone to overfitting than previously thought. This underscores the importance of a well tested and openly accessible baseline implementation like <i>AUSAXS</i>. <i>AUSAXS</i> is freely available at https://github.com/AUSAXS/AUSAXS.