@article {2018|2135,
	title = {Segmentation and the Entropic Elasticity of Modular Proteins},
	journal = {J Phys Chem Lett},
	volume = {9},
	year = {2018},
	month = {Aug},
	pages = {4707-4713},
	abstract = {<p>Single-molecule force spectroscopy utilizes polyproteins, which are composed of tandem modular domains, to study their mechanical and structural properties. Under the application of external load, the polyproteins respond by unfolding and refolding domains to acquire the most favored extensibility. However, unlike single-domain proteins, the sequential unfolding of the each domain modifies the free energy landscape (FEL) of the polyprotein nonlinearly. Here we use force-clamp (FC) spectroscopy to measure unfolding and collapse-refolding dynamics of polyubiquitin and poly(I91). Their reconstructed unfolding FEL involves hundreds of kB T in accumulating work performed against conformational entropy, which dwarfs the \&sim;30 kB T that is typically required to overcome the free energy difference of unfolding. We speculate that the additional entropic energy caused by segmentation of the polyprotein to individual proteins plays a crucial role in defining the \&quot;shock absorber\&quot; properties of elastic proteins such as the giant muscle protein titin.</p>
},
	doi = {10.1021/acs.jpclett.8b01925},
	author = {Berkovich, Ronen and Fernandez, Vicente I and Guillaume Stirnemann and Valle-Orero, Jessica and Fernandez, Julio M}
}
@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}
}
