1071-mHDX-MS: Mapping Protein Energy Landscapes

Paper Talk · Jun 3, 2026 · 23m

This paper describes mHDX-MS, a new high-throughput experimental technique used to map the protein energy landscapes of thousands of small protein domains simultaneously. While traditional structural biology focuses on stable native states, this study identifies the rare conformational fluctuations and higher-energy states that dictate how proteins function and aggregate. By analyzing over 5,000 domains, the researchers discovered significant variations in opening cooperativity, proving that proteins with identical folds can exhibit vastly different local stabilities. The authors utilized…