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Science 316 (5828): 1144-1148

Copyright © 2007 by the American Association for the Advancement of Science

Single-Molecule Experiments in Vitro and in Silico

Marcos Sotomayor, and Klaus Schulten*

Abstract: Single-molecule force experiments in vitro enable the characterization of the mechanical response of biological matter at the nanometer scale. However, they do not reveal the molecular mechanisms underlying mechanical function. These can only be readily studied through molecular dynamics simulations of atomic structural models: "in silico" (by computer analysis) single-molecule experiments. Steered molecular dynamics simulations, in which external forces are used to explore the response and function of macromolecules, have become a powerful tool complementing and guiding in vitro single-molecule experiments. The insights provided by in silico experiments are illustrated here through a review of recent research in three areas of protein mechanics: elasticity of the muscle protein titin and the extracellular matrix protein fibronectin; linker-mediated elasticity of the cytoskeleton protein spectrin; and elasticity of ankyrin repeats, a protein module found ubiquitously in cells but with an as-yet unclear function.

Department of Physics, University of Illinois at Urbana-Champaign, and Beckman Institute for Advanced Science and Technology, 405 North Mathews Avenue, Urbana, IL 61801, USA.

* To whom correspondence should be addressed. E-mail: kschulte{at}

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