@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 {2008|1603,
	title = {Diffusion of glycerol through Escherichia coli aquaglyceroporin GlpF},
	journal = {Biophys. J.},
	volume = {94},
	number = {3},
	year = {2008},
	pages = {832{\textendash}839},
	abstract = {The glycerol uptake facilitator, GlpF, a major intrinsic protein found in Escherichia coli, selectively conducts water and glycerol across the inner membrane. The free energy landscape characterizing the assisted transport of glycerol by this homotetrameric aquaglyceroporin has been explored by means of equilibrium molecular dynamics over a timescale spanning 0.12 micros. To overcome the free energy barriers of the conduction pathway, an adaptive biasing force is applied to the glycerol molecule confined in each of the four channels. The results illuminate the critical role played by intramolecular relaxation on the diffusion properties of the permeant. These free energy calculations reveal that glycerol tumbles and isomerizes on a timescale comparable to that spanned by its adaptive-biasing-force-assisted conduction in GlpF. As a result, reorientation and conformational equilibrium of glycerol in GlpF constitute a bottleneck in the molecular simulations of the permeation event. A profile characterizing the position-dependent diffusion of the permeant has been determined, allowing reaction rate theory to be applied for investigating conduction kinetics based on the measured free energy landscape.},
	keywords = {Aquaporins, Chemical, Computer Simulation, Diffusion, Escherichia coli Proteins, Glycerol, Ion Channel Gating, Models, Molecular, Molecular Conformation, Porosity},
	doi = {10.1529/biophysj.107.115105},
	author = {J{\'e}r{\^o}me H{\'e}nin and Emad Tajkhorshid and Klaus Schulten and Christophe Chipot}
}
