title: Bayesian estimates of free energies from nonequilibrium work data in the presence of instrument noise.
abstract: The Jarzynski equality and the fluctuation theorem relate equilibrium free energy differences to nonequilibrium measurements of the work. These relations extend to single-molecule experiments that have probed the finite-time thermodynamics of proteins and nucleic acids. The effects of experimental error and instrument noise have not been considered previously. Here, we present a Bayesian formalism for estimating free energy changes from nonequilibrium work measurements that compensates for instrument noise and combines data from multiple driving protocols. We reanalyze a recent set of experiments in which a single RNA hairpin is unfolded and refolded using optical tweezers at three different rates. Interestingly, the fastest and farthest-from-equilibrium measurements contain the least instrumental noise and, therefore, provide a more accurate estimate of the free energies than a few slow, more noisy, near-equilibrium measurements. The methods we propose here will extend the scope of single-molecule experiments; they can be used in the analysis of data from measurements with atomic force microscopy, optical, and magnetic tweezers.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. paul.maragakis@deshaw.com
authors.forename: Paul
authors.initials: P
authors.lastname: Maragakis
authors.forename: Felix
authors.initials: F
authors.lastname: Ritort
authors.forename: Carlos
authors.initials: C
authors.lastname: Bustamante
authors.forename: Martin
authors.initials: M
authors.lastname: Karplus
authors.forename: Gavin E
authors.initials: GE
authors.lastname: Crooks
mesh_terms: D001499:Bayes Theorem; D002623:Chemistry Techniques, Analytical / Q000295:instrumentation*; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry; D012107:Research Design; D013816:Thermodynamics
chemical_list: D012313:RNA