Significance
Comprehensive and accurate identification of SS in proteins is critical for elucidating protein structures and functions. Yet, it is far from routine to accomplish this task in many analytical or core laboratories. Numerous published methods require complex sample preparation methods, specialized mass spectrometers and cumbersome or proprietary software tools, thus cannot be easily implemented in unspecialized laboratories. Here, we describe a robust and rapid SS mapping approach that utilizes readily available reagents, instruments, and software; it can be easily implemented in any analytical core laboratories, and tested for its impact on the research community.