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Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520 USA
Correspondence: Address reprint requests to Gerhard Hummer, National Institutes of Health, Bldg. 5, Rm. 132, Bethesda, MD 20892. Tel.: 301-402-6290; Fax: 301-496-0825; E-mail: hummer{at}helix.nih.gov.
Mechanical forces exerted by laser tweezers or atomic force microscopes can be used to drive rare transitions in single molecules, such as unfolding of a protein or dissociation of a ligand. The phenomenological description of pulling experiments based on Bell's expression for the force-induced rupture rate is found to be inadequate when tested against computer simulations of a simple microscopic model of the dynamics. We introduce a new approach of comparable complexity to extract more accurate kinetic information about the molecular events from pulling experiments. Our procedure is based on the analysis of a simple stochastic model of pulling with a harmonic spring and encompasses the phenomenological approach, reducing to it in the appropriate limit. Our approach is tested against computer simulations of a multimodule titin model with anharmonic linkers and then an illustrative application is made to the forced unfolding of I27 subunits of the protein titin. Our procedure to extract kinetic information from pulling experiments is simple to implement and should prove useful in the analysis of experiments on a variety of systems.
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