Theory, analysis, and interpretation of single-molecule force spectroscopy experiments.
Dynamic force spectroscopy probes the kinetic and thermodynamic properties of single molecules and molecular assemblies. Here, we propose a simple procedure to extract kinetic information from such experiments. The cornerstone of our method is a transformation of the rupture-force histograms obtained at different force-loading rates into the force-dependent lifetimes measurable in constant-force experiments. To interpret the force-dependent lifetimes, we derive a generalization of Bell's formula that is formally exact within the framework of Kramers theory. This result complements the analytical expression for the lifetime that we derived previously for a class of model potentials. We illustrate our procedure by analyzing the nanopore unzipping of DNA hairpins and the unfolding of a protein attached by flexible linkers to an atomic force microscope. Our procedure to transform rupture-force histograms into the force-dependent lifetimes remains valid even when the molecular extension is a poor reaction coordinate and higher-dimensional free-energy surfaces must be considered. In this case the microscopic interpretation of the lifetimes becomes more challenging because the lifetimes can reveal richer, and even nonmonotonic, dependence on the force.
Dudko
Olga K
OK
Department of Physics and Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, CA 92093, USA. dudko@physics.ucsd.edu
Hummer
Gerhard
G
Szabo
Attila
A
D004247:DNA / Q000737:chemistry; D006207:Half-Life; D007700:Kinetics; D018625:Microscopy, Atomic Force / Q000379:methods*; D009038:Motion; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D017510:Protein Folding; D013816:Thermodynamics
D004247:DNA