The Physics department colloquia are usually on Friday afternoons at 3:30 pm in Lapham Hall Room 160. Coffee and cookies are served at 3:15 pm in the same room. Anyone is welcome.

The Effect of Mechanical Force on the Free-Energy Landscape of Proteins in Single Molecule Experimens
Dr. Ronen Berkovich, Asst. Professor, Dept. of Chemical Engineering & the Ilze Katz Institute for Nanoscience and Technology, Ben-Gurion Univ. of the Negev (Israel)

Single-molecule force spectroscopy has opened up new approaches to the study of protein dynamics. For example, the folding of an extended protein after an abrupt quench in the pulling force was shown to follow variable collapse trajectories marked by well-defined stages. Curiously, these traces display a track that departs from the expected two-state folding behavior commonly observed in bulk. Nonetheless, this observation can be explained by plain considerations about the free energy, which indicates the formation of a generic entropic barrier under the application of an external force. The resulting one-dimensional free energy of the molecule display a force-dependent energy barrier of magnitude, ΔE = ε(F – Fc)3/2. This barrier separates the collapsed state of the unfolded protein from a force-driven extended conformation that vanishes at a critical force Fc. The long distance to transition characterizing this barrier makes it highly sensitive to the applied force, and consequently to the kinetics of crossing it. Brownian dynamics simulations incorporating this one dimensional potential-of-mean-force (PMF) replicates the experimental observations. Interestingly, these simulations also reproduce experiments of single proteins under force, which report rapid transition between two states (interpreted as folded/unfolded). Thus raising the question around which barriers do these hopping take place. To better understand this phenomenon observed in proteins under force, we performed Molecular dynamics simulations of a model protein (GB1) in explicit solvent. From these simulations the protein’s multidimensional PMF was reconstructed, unambiguously showing the separation of (more than two) thermodynamic states within it. Projecting this PMF over the single end-to-end length reaction coordinate monitored in force spectroscopy experiments depicts a contour similar to the one proposed by the phenomenological model.