AlphaSAXS: Reconstructing Protein Structure with Physiologically Relevant Conformations from X-ray Scattering Data

AlphaFold has revolutionized structural biology with accurate protein predictions, yet challenges remain due to the dynamic nature of proteins. Over 40% of human proteins have flexible regions crucial in diseases like Alzheimer's and COVID-19. To overcome AlphaFold's limitations, we integrated small-angle X-ray scattering (SAXS) data, leveraging its ability to provide structural insights on flexible macromolecules. Using computationally generated SAXS data to inform network inputs during fine-tuning and inference, we enhanced AlphaFold to improve conformation predictions for flexible protein regions. This approach can advance our understanding of experimentally guided structural prediction and provides a potential solution for improving computational prediction of physiologically relevant conformations.