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Extracting the Hidden Distributions Underlying the Mean Transition State Structures in Protein Folding
, Gopi S., Paul S., Ranu S.
Published in American Chemical Society
Volume: 9
Issue: 7
Pages: 1771 - 1777
The inherent conflict between noncovalent interactions and the large conformational entropy of the polypeptide chain forces folding reactions and their mechanisms to deviate significantly from chemical reactions. Accordingly, measures of structure in the transition state ensemble (TSE) are strongly influenced by the underlying distributions of microscopic folding pathways that are challenging to discern experimentally. Here, we present a detailed analysis of 150,000 folding transition paths of five proteins at three different thermodynamic conditions from an experimentally consistent statistical mechanical model. We find that the underlying TSE structural distributions are rarely unimodal, and the average experimental measures arise from complex underlying distributions. Unfolding pathways also exhibit subtle differences from folding counterparts due to a combination of Hammond behavior and native-state movements. Local interactions and topological complexity, to a lesser extent, are found to determine pathway heterogeneity, underscoring the importance of the balance between local and nonlocal energetics in protein folding. © 2018 American Chemical Society.
About the journal
JournalData powered by TypesetJournal of Physical Chemistry Letters
PublisherData powered by TypesetAmerican Chemical Society
Open AccessNo