pnas Proc Natl Acad Sci U S A PNAS 0027-8424 The National Academy of Sciences 071034098 0340 10.1073/pnas.071034098 11274384 Physical Sciences Chemistry Biological Sciences Biophysics Free energy reconstruction from nonequilibrium single-molecule pulling experiments Hummer Gerhard * Szabo Attila Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520

To whom reprint requests should be addressed at: LCP/NIDDK, Bldg. 5, Rm. 132, National Institutes of Health, Bethesda, MD 20892-0520. E-mail: hummer@helix.nih.gov.

Communicated by David Chandler, University of California, Berkeley, CA

27 3 2001 98 7 3658 3661
28 11 2000
22 1 2001
Copyright © 2001, The National Academy of Sciences 2001 See commentary on page 3636.

Laser tweezers and atomic force microscopes are increasingly used to probe the interactions and mechanical properties of individual molecules. Unfortunately, using such time-dependent perturbations to force rare molecular events also drives the system away from equilibrium. Nevertheless, we show how equilibrium free energy profiles can be extracted rigorously from repeated nonequilibrium force measurements on the basis of an extension of Jarzynski's remarkable identity between free energies and the irreversible work.

This can be seen in the following summation: ∑ m p ˙ m = 0

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