Fast calculation of small-angle scattering profiles of dense protein solutions modeled at the all-atom level

• 成果类型: Article
• 署名作者: Qin, Sanbo; Zhou, Huan- Xiang
• 署名单位: University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14242
• DOI: 10.1073/pnas.2519265122
• 发表日期: 2025-09-30
• 关键词: x-ray-scattering; fft-based method; phase-separation; web server; saxs; computation; benchmarking; instrument; lysozyme; binding

摘要

The small-angle scattering (SAS) profile of a dense protein solution contains rich information about interprotein interactions, but extracting this information has been extremely challenging. In previous studies, we developed a fast Fourier transform-based method, FMAPB2, to compute protein pair interactions at the all-atom level. Here, we use FMAPB2 to precompute pair interaction energies and then use the latter to drive simulations of dense protein solutions. The resulting MAEPPI (many-protein atomistic energy from precomputed pair interaction) enables simulations of atomistic proteins at the speed of Lennard-Jones particles. On snapshots sampled from the simulations, we directly calculate the SAS profile. The results reveal artifacts generated by widely used spherical models and support a significant dimer population of bovine serum albumin at high concentrations. Our approach promises to modernize the prediction and interpretation of SAS profiles of dense protein solutions.