title: Transient violations of the second law of thermodynamics in protein unfolding examined using synthetic atomic force microscopy and the fluctuation theorem.
abstract: The synthetic atomic force microscopy (AFM) method is developed to simulate a periodically replicated atomistic system subject to force and length fluctuations characteristic of an AFM experiment. This new method is used to examine the forced-extension and subsequent rupture of the alpha-helical linker connecting periodic images of a spectrin protein repeat unit. A two-dimensional potential of mean force (PMF) along the length and a reaction coordinate describing the state of the linker was calculated. This PMF reveals that the basic material properties of the spectrin repeat unit are sensitive to the state of linker, an important feature that cannot be accounted for in a one-dimensional PMF. Furthermore, nonequilibrium simulations were generated to examine the rupture event in the context of the fluctuation theorem. These atomistic simulations demonstrate that trajectories which are in apparent violation of the second law can overcome unfolding barriers at significantly reduced rupture forces.
authors.affiliation: Center for Biophysical Modeling and Simulation and Department of Chemistry, University of Utah, Salt Lake City, Utah 84112-0850, USA.
authors.forename: Sterling
authors.initials: S
authors.lastname: Paramore
authors.forename: Gary S
authors.initials: GS
authors.lastname: Ayton
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
mesh_terms: D003198:Computer Simulation; D006860:Hydrogen Bonding; D018625:Microscopy, Atomic Force; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000648:ultrastructure; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D046912:Multiprotein Complexes