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This lecture covers the techniques and applications of synchrotrons and x-ray free-electron lasers in macromolecular crystallography. The instructor explains the phase problem for large molecules, detailing approaches like multiple isomorphous replacement, multiwavelength anomalous dispersion, and single-wavelength anomalous diffraction. Various macromolecular crystallography approaches are discussed, including Multiple/Single Isomorphous Replacement, Multiwavelength Anomalous Dispersion, and Single-Wavelength Anomalous Diffraction. The lecture also explores trends in MX phasing techniques, such as MIR, SIR, and MAD. Practical examples like the COVID-19 main protease and Benzylpenicillin are used to illustrate the concepts.