title: Unfolding dynamics of proteins under applied force.
abstract: Understanding the mechanisms of protein folding is a major challenge that is being addressed effectively by collaboration between researchers in the physical and life sciences. Recently, it has become possible to mechanically unfold proteins by pulling on their two termini using local force probes such as the atomic force microscope. Here, we present data from experiments in which synthetic protein polymers designed to mimic naturally occurring polyproteins have been mechanically unfolded. For many years protein folding dynamics have been studied using chemical denaturation, and we therefore firstly discuss our mechanical unfolding data in the context of such experiments and show that the two unfolding mechanisms are not the same, at least for the proteins studied here. We also report unexpected observations that indicate a history effect in the observed unfolding forces of polymeric proteins and explain this in terms of the changing number of domains remaining to unfold and the increasing compliance of the lengthening unstructured polypeptide chain produced each time a domain unfolds.
authors.affiliation: Department of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, UK. d.a.m.smith@leeds.ac.uk
authors.forename: D Alastair
authors.initials: DA
authors.lastname: Smith
authors.forename: David J
authors.initials: DJ
authors.lastname: Brockwell
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Zinober
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Blake
authors.forename: Godfrey S
authors.initials: GS
authors.lastname: Beddard
authors.forename: Peter D
authors.initials: PD
authors.lastname: Olmsted
authors.forename: Sheena E
authors.initials: SE
authors.lastname: Radford
mesh_terms: D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009010:Monte Carlo Method; D011489:Protein Denaturation; D017510:Protein Folding; D013314:Stress, Mechanical; D013696:Temperature