Large-scale discovery, analysis, and design of protein energy landscapes.

ABSTRACT: All folded proteins continuously fluctuate between their low-energy native structures and higher energy conformations that can be partially or fully unfolded. These rare states influence protein function, interactions, aggregation, and immunogenicity, yet they remain far less understood than protein native states. Although native protein structures are now often predictable with impressive accuracy, conformational fluctuations and their energies remain largely invisible and unpredictable, and experimental challenges have prevented large-scale measurements that could improve machine learning and physics-based modeling. Here, we introduce a multiplexed experimental approach to analyze the energies of conformational fluctuations for hundreds of protein domains in parallel using intact protein

SUBMITTER: Ferrari AJR 

PROVIDER: S-EPMC11974690 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature