Origin of Internal Friction in Disordered Proteins Depends on Solvent Quality

Wenwei Zheng, Hagen Hofmann, Benjamin Schuler, Robert B. Best

    Research output: Contribution to journalArticlepeer-review

    15 Scopus citations


    Protein dynamics often exhibit internal friction; i.e., contributions to friction that cannot solely be attributed to the viscosity of the solvent. Remarkably, even unfolded and intrinsically disordered proteins (IDPs) exhibit this behavior, despite typically being solvent-exposed. Several competing molecular mechanisms have been suggested to underlie this phenomenon, in particular dihedral relaxation and intrachain interactions. It has also recently been shown that single-molecule data reflecting internal friction in the disordered protein ACTR cannot be explained using polymer models unless this friction is dependent on protein collapse. However, the connection between the collapse of the chain and the underlying mechanism of internal friction has been unclear. To address this issue, we combine molecular simulation and single-molecule experimental data to investigate how chain compaction affects protein dynamics in the context of ACTR. Chain reconfiguration times and internal friction estimated from all-atom simulations are in semiquantitative agreement with experimental data. We dissect the underlying molecular mechanism with all-atom and coarse-grained simulations and clearly identify both intrachain interactions and dihedral angle transitions as contributions to internal friction. However, their relative contribution is strongly dependent on the compactness of the IDP; while dihedral relaxation dominates internal friction in expanded configurations, intrachain interactions dominate for more compact chains. Our results thus imply a continuous transition between mechanisms and provide a link between internal friction in IDPs and that in more compact and folded states of proteins.

    Original languageEnglish (US)
    Pages (from-to)11478-11487
    Number of pages10
    JournalJournal of Physical Chemistry B
    Issue number49
    StatePublished - Dec 13 2018

    ASJC Scopus subject areas

    • Physical and Theoretical Chemistry
    • Surfaces, Coatings and Films
    • Materials Chemistry


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