ArticleProceedings of the National Academy of Sciences of the United States of America2022
Exact reaction coordinates for flap opening in HIV-1 protease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Identification and understanding of allostery hotspots in proteins: Integration of deep mutational scanning and multi-faceted computational analyses.Journal of molecular biology · 2025Review
- Reaction Coordinates Are Optimal Channels of Energy Flow.Annual review of physical chemistry · 2025Review
- Enhanced sampling of protein conformational changes via true reaction coordinates from energy relaxation.Nature communications · 2025Article
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Authors and funding
3 authors.
Funding
Abstract
The primary goal of protein science is to understand how proteins function, which requires understanding the functional dynamics responsible for transitions between different functional structures of a protein. A central concept is the exact reaction coordinates that can determine the value of committor for any protein configuration, which provide the optimal description of functional dynamics. Despite intensive efforts, identifying the exact reaction coordinates (RCs) in complex molecules remains a formidable challenge. Using the recently developed generalized work functional, we report the discovery of the exact RCs for an important functional process-the flap opening of HIV-1 protease. Our results show that this process has six RCs, each one is a linear combination of ~240 backbone dihedrals, providing the precise definition of collectivity and cooperativity in the functional dynamics of a protein. Applying bias potentials along each RC can accelerate flap opening by [Formula: see text] to [Formula: see text] folds. The success in identifying the RCs of a protein with 198 residues represents a significant progress beyond that of the alanine dipeptide, currently the only other complex molecule for which the exact RCs for its conformational changes are known. Our results suggest that the generalized work functional (GWF) might be the fundamental operator of mechanics that controls protein dynamics.
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