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Abstract

The 13A biological small- and wide-angle X-ray scattering (SWAXS) beamline at the Taiwan Photon Source (TPS) is equipped with dual in-vacuum detectors and an integrated online size-exclusion chromatography (SEC) system, enabling the investigation of biomolecular structures and compositions in physiological solution across a broad range of length scales. When coupled with molecular dynamics (MD) simulations, this SWAXS-MD approach facilitates the reconstruction of all-atom models of biomolecules, capturing their domain interfaces and hydration shell structures in detail. Using this methodology, we showcase several successful biomedical applications: elucidating binding structures and efficacies of protein-drug complexes in solution, distinguishing serum protein conformations in a series of medicated serum samples from a lupus nephritis (LN) patient, and characterizing drug loading and trigger-release structural changes in liposomes and copolymer micelles, and gene-loaded lipid nanoparticles. In conjunction with laboratory-based SEC-MALS-DLS measurements, the TPS SEC-SWAXS platform provides molecular-level characterizations in biomedical research and industrial applications, and offers potential for early diagnosis of serum protein relevant diseases, as well as rapid structural controls of nanoscale drug delivery systems.