Structure determination from single-molecule X-ray scattering images using stochastic gradient ascent
Abstract
Scattering experiments using ultrashort X-ray free electron laser (XFEL) pulses have opened a new path for structure determination of a wide variety of specimens, including nano-crystals and entire viruses, approaching atomistic spatial and femtoseconds time resolution. However, random and unknown sample orientations as well as low signal to noise ratios have so far prevented a successful application to smaller specimens like single biomolecules. We here present resolution-annealed stochastic gradient ascent (RASTA), a new approach for direct atomistic electron density determination, which utilizes our recently developed rigorous Bayesian treatment of single-particle X-ray scattering. We demonstrate electron density determination at 2\r{A} resolution of various small proteins from synthetic scattering images with as low as 15 photons per image.
Cite
@article{arxiv.2505.05109,
title = {Structure determination from single-molecule X-ray scattering images using stochastic gradient ascent},
author = {Steffen Schultze and D. Russell Luke and Helmut Grubmüller},
journal= {arXiv preprint arXiv:2505.05109},
year = {2026}
}
Comments
24 pages, 6 figures