title: Dynamic disorder can explain non-exponential kinetics of fast protein mechanical unfolding.
abstract: Protein unfolding often does not obey a simple two-state behavior. Previous single molecule force spectroscopy studies demonstrated stretched exponential kinetics of protein unfolding under a constant pulling force, the molecular origin of which remains subject to debate. We here set out to extensively sample the mechanical unfolding of ubiquitin and NuG2 by Molecular Dynamics (MD) simulations. Both proteins show kinetics best fit by stretched exponentials, with stretching exponents similar to those found in experiments, even though static disorder is absent in our short MD simulations. Instead, we can ascribe non-exponential kinetics to dynamic disorder, due to conformational fluctuations on the nanosecond timescale. Our study highlights the general role of dynamic disorder in protein kinetics on a broad range of time scales even including those probed in MD simulations.
authors: Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany.
authors: Bogdan I
authors: BI
authors: Costescu
authors: Institute for Theoretical Physics, Leipzig University, Postfach 100920, 04009 Leipzig, Germany.
authors: Sebastian
authors: S
authors: Sturm
authors: Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany; Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Im Neuenheimer Feld 368, 69120 Heidelberg, Germany. Electronic address: frauke.graeter@h-its.org.
authors: Frauke
authors: F
authors: Gräter
mesh_terms: D007700:Kinetics; D018625:Microscopy, Atomic Force / Q000379:methods; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry*; D000072760:Single Molecule Imaging; D025801:Ubiquitin / Q000737:chemistry*
chemical_list: D011506:Proteins; D025801:Ubiquitin
keywords: Atomic force microscopy; Molecular Dynamics simulations; Non-exponential kinetics; NuG2; Ubiquitin