Verification of the Crooks fluctuation theorem and recovery of RNA folding free energies

By D. Collin, Felix Ritort, Christopher Jarzynski, S. Smith, Ignacio Tinoco Jr., Carlos Bustamante. Nature, 2005

875 citations recorded by the source corpus.

Atomic force microscopes and optical tweezers are widely used to probe the mechanical properties of individual molecules and molecular interactions, by exerting mechanical forces that induce transitions such as unfolding or dissociation. These transitions often occur under nonequilibrium conditions and are associated with hysteresis effects—features usually taken to preclude the extraction of equilibrium information from the experimental data. But fluctuation theorems allow us to relate the work along nonequilibrium trajectories to thermodynamic free-energy differences. They have been shown to be applicable to single-molecule force measurements and have already provided information on the folding free energy of a RNA hairpin. Here we show that the Crooks fluctuation theorem can be used to determine folding free energies for folding and unfolding processes occurring in weak as well as strong nonequilibrium regimes, thereby providing a test of its validity under such conditions. We use optical tweezers to measure repeatedly the mechanical work associated with the unfolding and refolding of a small RNA hairpin and an RNA three-helix junction. The resultant work distributions are then analysed according to the theorem and allow us to determine the difference in folding free energy between an RNA molecule and a mutant differing only by one base pair, and the thermodynamic stabilizing effect of magnesium ions on the RNA structure.

Subfields: Biomedical Engineering, Physical and Theoretical Chemistry, Statistical and Nonlinear Physics

View Paper: https://www.semanticscholar.org/paper/136a9542498d470d172cd1e5a860adb2345ec59c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biomedical Engineering

In Physical and Theoretical Chemistry

In Statistical and Nonlinear Physics

Citations in the corpus

Experimental test of the quantum Jarzynski equality with a trapped-ion system (2014, methodology): “For example, the method can be immediately used to the test of Crooks’ relation in quantum regime [2, 5] and to further investigations of the equality in an open quantum system [17, 20].”
Stochastic thermodynamics: From principles to the cost of precision (2017, background): “For the beautiful first experimental application of this relation with biomolecules, see [22].”
Colloquium : Statistical mechanics and thermodynamics at strong coupling: Quantum and classical (2019, background): “While the work as a fluctuating quantity can be expressed in an experimentally accessible way for classical systems (Collin et al., 2005), in quantum systems the TPPEMS of the total energy presents a major experimental challenge (An et al.”
Nonequilibrium fluctuations, fluctuation theorems, and counting statistics in quantum systems (2008, background): “Work fluctuations have been studied in macromolecule pulling experiments [40, 124] and in optically driven microspheres [182], entropy fluctuations have also been measured in a similar system [188] and in spectroscopic experiments on a defect center in diamond [159, 179].”
Colloquium : Quantum heat transport in condensed matter systems (2021, background): “Two main classes of systems under study have been those in the seminal experiments on molecules (Collin et al., 2005) and on electrical circuits (Bérut et al., 2016; Ciliberto et al., 2013; Küng et al., 2012; Pekola, 2015; Saira et al., 2012b).”
Nonequilibrium fluctuations in small systems: From physics to biology (2007, background): “This is important in either experiments [101] or simulations [118, 119] where it is convenient and natural to use data from the forward and reverse process.”
Description of quantum coherence in thermodynamic processes requires constraints beyond free energy (2014, background): “Sa(r||s) is simply the quantum relative entropy30 and the constraints of equation (1) reduce to DFr0, where F(r)1⁄4Tr[rH] kTS(r).”
Near-optimal protocols in complex nonequilibrium transformations (2016, background): “Phys Rev E Stat Nonlin Soft Matter Phys 91(3):032104.”