鄭有舜

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 mRNA-loaded lipid nanoparticles. In conjunction with laboratory-based SEC-MALS-DLS measurements, the SEC-SWAXS platform provides molecular-level characterizations for both biomedical research and industrial applications, and offers potential for early diagnosis of serum protein relevant diseases, as well as rapid structural characterization and quality control of nanoscale drug delivery systems.

Keywords – Solution structures and compositions, biomolecules, protein and liposome, SEC-SWAXS, SEC-MALS-DLS

 Back