Bayesian estimates of free energies from nonequilibrium work data in the presence of instrument noise.
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.
Maragakis
Paul
P
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. paul.maragakis@deshaw.com
Ritort
Felix
F
Bustamante
Carlos
C
Karplus
Martin
M
Crooks
Gavin E
GE
D001499:Bayes Theorem; D002623:Chemistry Techniques, Analytical / Q000295:instrumentation*; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry; D012107:Research Design; D013816:Thermodynamics
D012313:RNA