@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}
}
@article {2013|1689,
	title = {When Does Trimethylamine <italic>N</italic>-Oxide Fold a Polymer Chain and Urea Unfold It?},
	journal = {J. Phys. Chem. B},
	volume = {117},
	year = {2013},
	pages = {8723{\textendash}8732},
	abstract = {<p>Longstanding mechanistic questions about the role of protecting osmolyte trimethylamine N-oxide (TMAO) that favors protein folding and the denaturing osmolyte urea are addressed by studying their effects on the folding of uncharged polymer chains. Using atomistic molecular dynamics simulations, we show that 1 M TMAO and 7 M urea solutions act dramatically differently on these model polymer chains. Their behaviors are sensitive to the strength of the attractive dispersion interactions of the chain with its environment: when these dispersion interactions are sufficiently strong, TMAO suppresses the formation of extended conformations of the hydrophobic polymer as compared to water while urea promotes the formation of extended conformations. Similar trends are observed experimentally for real protein systems. Quite surprisingly, we find that both protecting and denaturing osmolytes strongly interact with the polymer, seemingly in contrast with existing explanations of the osmolyte effect on proteins. We show that what really matters for a protective osmolyte is its effective depletion as the polymer conformation changes, which leads to a negative change in the preferential binding coefficient. For TMAO, there is a much more favorable free energy of insertion of a single osmolyte near collapsed conformations of the polymer than near extended conformations. By contrast, urea is preferentially stabilized next to the extended conformation and thus has a denaturing effect.</p>},
	isbn = {15206106},
	url = {http://pubs.acs.org/doi/abs/10.1021/jp405609j$\backslash$nhttp://pubs.acs.org/doi/pdf/10.1021/jp405609j$\backslash$nhttp://dx.doi.org/10.1021/jp405609j},
	author = {Mondal, Jagannath and Guillaume Stirnemann and Berne, B J}
}
