@article {2014|1751,
	title = {How force unfolding differs from chemical denaturation.},
	journal = {Proc. Natl. Acad. Sci. U.s.a},
	volume = {111},
	year = {2014},
	pages = {3413{\textendash}8},
	abstract = {<p>Single-molecule force spectroscopies are remarkable tools for studying protein folding and unfolding, but force unfolding explores protein configurations that are potentially very different from the ones traditionally explored in chemical or thermal denaturation. Understanding these differences is crucial because such configurations serve as starting points of folding studies, and thus can affect both the folding mechanism and the kinetics. Here we provide a detailed comparison of both chemically induced and force-induced unfolded state ensembles of ubiquitin based on extensive, all-atom simulations of the protein either extended by force or denatured by urea. As expected, the respective unfolded states are very different on a macromolecular scale, being fully extended under force with no contacts and partially extended in urea with many nonnative contacts. The amount of residual secondary structure also differs: A significant population of $\alpha$-helices is found in chemically denatured configurations but such helices are absent under force, except at the lowest applied force of 30 pN where short helices form transiently. We see that typical-size helices are unstable above this force, and $\beta$-sheets cannot form. More surprisingly, we observe striking differences in the backbone dihedral angle distributions for the protein unfolded under force and the one unfolded by denaturant. A simple model based on the dialanine peptide is shown to not only provide an explanation for these striking differences but also illustrates how the force dependence of the protein dihedral angle distributions give rise to the worm-like chain behavior of the chain upon force.</p>},
	keywords = {Chemical, Hydrogen-Ion Concentration, Models, Molecular Dynamics Simulation, Protein Conformation, Protein Denaturation, Protein Folding, Protein Unfolding, Ubiquitin, Ubiquitin: chemistry, Urea, Urea: chemistry},
	issn = {1091-6490},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24550471},
	author = {Guillaume Stirnemann and Kang, Seung-gu and Zhou, Ruhong and Berne, Bruce J}
}
@article {2013|1752,
	title = {Elasticity, structure, and relaxation of extended proteins under force.},
	journal = {Proc. Natl. Acad. Sci. U.s.a},
	volume = {110},
	year = {2013},
	pages = {3847{\textendash}52},
	abstract = {<p>Force spectroscopies have emerged as a powerful and unprecedented tool to study and manipulate biomolecules directly at a molecular level. Usually, protein and DNA behavior under force is described within the framework of the worm-like chain (WLC) model for polymer elasticity. Although it has been surprisingly successful for the interpretation of experimental data, especially at high forces, the WLC model lacks structural and dynamical molecular details associated with protein relaxation under force that are key to the understanding of how force affects protein flexibility and reactivity. We use molecular dynamics simulations of ubiquitin to provide a deeper understanding of protein relaxation under force. We find that the WLC model successfully describes the simulations of ubiquitin, especially at higher forces, and we show how protein flexibility and persistence length, probed in the force regime of the experiments, are related to how specific classes of backbone dihedral angles respond to applied force. Although the WLC model is an average, backbone model, we show how the protein side chains affect the persistence length. Finally, we find that the diffusion coefficient of the protein{\textquoteright}s end-to-end distance is on the order of 10(8) nm(2)/s, is position and side-chain dependent, but is independent of the length and independent of the applied force, in contrast with other descriptions.</p>},
	keywords = {Atomic Force, Biophysical Phenomena, Computer Simulation, Elasticity, Mechanical, Microscopy, Models, Molecular, Molecular Dynamics Simulation, Proteins, Proteins: chemistry, Stress, Ubiquitin, Ubiquitin: chemistry},
	issn = {1091-6490},
	url = {http://www.pnas.org/content/early/2013/02/13/1300596110.abstract},
	author = {Guillaume Stirnemann and Giganti, David and Fernandez, Julio M and Berne, B J}
}
