Deciphering In-vivo Cross-linking Mass Spectrometry Data for Dynamic Protein Structure Analysis

Protein structure and protein-protein interactions(PPIs) are crucial for regulating cellular activities required for cell viability and homeostasis. Chemical cross-linking coupled with mass spectrometry(CXMS) has become a versatile tool providing insights into both protein structure with distance restraints and protein-protein interactions with interface sites. Cross-links as the most information-rich data in a CXMS experiment are responsible for the structural model validation and integrative modeling with high throughput and sensitivity. In this work, ensemble refinement of the existing protein structure against the in-vivo cross-linking distance restraints was performed for dynamic protein structure modeling and protein interaction binding interface building in the intracellular environment. These results indicate great potential of in-vivo CXMS data for providing a molecular basis of protein structural dynamics exploration and function performance.