Experimentally determined three-dimensional structures provide valuable molecular insights for structure-guided drug discovery, mechanistic investigation, and protein engineering. X-ray crystallography remains the most extensively represented experimental structure-determination method in the Protein Data Bank, accounting for approximately 80% of currently archived structures. Successful...

For decades, KRAS was considered one of oncology’s most difficult drug targets. In 2013, crystallographic studies revealed a previously unrecognized pocket beneath the switch-II region of KRAS G12C, providing a structural basis for mutant-selective inhibitor design. Years of medicinal chemistry and clinical development followed, culminating in the first FDA approval of a KRAS G12C...