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Conformational kinetics reveals affinities of protein conformational states
- Daniels, Kyle G., Suo, Yang, Oas, Terrence G.
- Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.30 pp. 9352-9357
- binding capacity, drugs, nucleic acids, proteins
- Despite 50 years of studies of coupled binding and conformational change reactions in proteins and nucleic acids, there has been no detailed analysis of the affinities of the multiple conformational states involved. The relationship between these affinities and the dynamics of conformational change has also been largely overlooked. We perform rigorous kinetic analysis of protein conformational change coupled to binding to concomitantly determine binding affinities of individual conformational states and rate constants for conformational changes. The results point to an inextricable link between affinities of the individual states and the change in conformational dynamics upon binding. The difference in affinities of conformational states is critical for driving conformational change and has implications in molecular recognition, allostery, and drug development.