Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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}ks.uiuc.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds.
C.-y. Lee, J. Lou, K.-k. Wen, M. McKane, S. G. Eskin, S. Ono, S. Chien, P. A. Rubenstein, C. Zhu, and L. V. McIntire (2013)
PNAS 110, 5022-5027
   Abstract »    Full Text »    PDF »
Direct observation of proteolytic cleavage at the S2 site upon forced unfolding of the Notch negative regulatory region.
N. L. Stephenson and J. M. Avis (2012)
PNAS 109, E2757-E2765
   Abstract »    Full Text »    PDF »
Rate limit of protein elastic response is tether dependent.
R. Berkovich, R. I. Hermans, I. Popa, G. Stirnemann, S. Garcia-Manyes, B. J. Berne, and J. M. Fernandez (2012)
PNAS 109, 14416-14421
   Abstract »    Full Text »    PDF »
Mutation of Conserved Histidines Alters Tertiary Structure and Nanomechanics of Consensus Ankyrin Repeats.
W. Lee, J. Strumpfer, V. Bennett, K. Schulten, and P. E. Marszalek (2012)
J. Biol. Chem. 287, 19115-19121
   Abstract »    Full Text »    PDF »
Cytosine methylation alters DNA mechanical properties.
P. M. D. Severin, X. Zou, H. E. Gaub, and K. Schulten (2011)
Nucleic Acids Res. 39, 8740-8751
   Abstract »    Full Text »    PDF »
The Giant Protein Titin: A Regulatory Node That Integrates Myocyte Signaling Pathways.
M. Kruger and W. A. Linke (2011)
J. Biol. Chem. 286, 9905-9912
   Abstract »    Full Text »    PDF »
Full Reconstruction of a Vectorial Protein Folding Pathway by Atomic Force Microscopy and Molecular Dynamics Simulations.
W. Lee, X. Zeng, H.-X. Zhou, V. Bennett, W. Yang, and P. E. Marszalek (2010)
J. Biol. Chem. 285, 38167-38172
   Abstract »    Full Text »    PDF »
Force-induced formation and propagation of adhesion nanodomains in living fungal cells.
D. Alsteens, M. C. Garcia, P. N. Lipke, and Y. F. Dufrene (2010)
PNAS 107, 20744-20749
   Abstract »    Full Text »    PDF »
Water's role in the force-induced unfolding of ubiquitin.
J. Li, J. M. Fernandez, and B. J. Berne (2010)
PNAS 107, 19284-19289
   Abstract »    Full Text »    PDF »
Structural insights into retinitis pigmentosa from unfolding simulations of rhodopsin mutants.
F. Fanelli and M. Seeber (2010)
FASEB J 24, 3196-3209
   Abstract »    Full Text »    PDF »
Exploring Transmembrane Diffusion Pathways With Molecular Dynamics.
Y. Wang, S. A. Shaikh, and E. Tajkhorshid (2010)
Physiology 25, 142-154
   Abstract »    Full Text »    PDF »
The Giant Protein Titin as an Integrator of Myocyte Signaling Pathways.
W. A. Linke and M. Kruger (2010)
Physiology 25, 186-198
   Abstract »    Full Text »    PDF »
PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis.
A. Grinthal, I. Adamovic, B. Weiner, M. Karplus, and N. Kleckner (2010)
PNAS 107, 2467-2472
   Abstract »    Full Text »    PDF »
Computational and single-molecule force studies of a macro domain protein reveal a key molecular determinant for mechanical stability.
D. L. Guzman, A. Randall, P. Baldi, and Z. Guan (2010)
PNAS 107, 1989-1994
   Abstract »    Full Text »    PDF »
The Roles of Pore Ring and Plug in the SecY Protein-conducting Channel.
J. Gumbart and K. Schulten (2008)
J. Gen. Physiol. 132, 709-719
   Abstract »    Full Text »    PDF »
Dissociation of minor groove binders from DNA: insights from metadynamics simulations.
A. V. Vargiu, P. Ruggerone, A. Magistrato, and P. Carloni (2008)
Nucleic Acids Res. 36, 5910-5921
   Abstract »    Full Text »    PDF »
Single molecule force spectroscopy reveals engineered metal chelation is a general approach to enhance mechanical stability of proteins.
Y. Cao, T. Yoo, and H. Li (2008)
PNAS 105, 11152-11157
   Abstract »    Full Text »    PDF »
Electrostatic funneling of substrate in mitochondrial inner membrane carriers.
Y. Wang and E. Tajkhorshid (2008)
PNAS 105, 9598-9603
   Abstract »    Full Text »    PDF »
BIOPHYSICS: Enigmas of Blood Clot Elasticity.
J. W. Weisel (2008)
Science 320, 456-457
   Abstract »    Full Text »    PDF »
Peptide adsorption on a hydrophobic surface results from an interplay of solvation, surface, and intrapeptide forces.
D. Horinek, A. Serr, M. Geisler, T. Pirzer, U. Slotta, S. Q. Lud, J. A. Garrido, T. Scheibel, T. Hugel, and R. R. Netz (2008)
PNAS 105, 2842-2847
   Abstract »    Full Text »    PDF »
Unique elastic properties of the spectrin tetramer as revealed by multiscale coarse-grained modeling.
D. T. Mirijanian and G. A. Voth (2008)
PNAS 105, 1204-1208
   Abstract »    Full Text »    PDF »
Hierarchies, multiple energy barriers, and robustness govern the fracture mechanics of {alpha}-helical and beta-sheet protein domains.
T. Ackbarow, X. Chen, S. Keten, and M. J. Buehler (2007)
PNAS 104, 16410-16415
   Abstract »    Full Text »    PDF »
Forced Unfolding of Proteins Within Cells.
C. P. Johnson, H.-Y. Tang, C. Carag, D. W. Speicher, and D. E. Discher (2007)
Science 317, 663-666
   Abstract »    Full Text »    PDF »
Forces and Bond Dynamics in Cell Adhesion.
E. A. Evans and D. A. Calderwood (2007)
Science 316, 1148-1153
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882