Folding and Unfolding of an Elastinlike Oligopeptide: “Inverse Temperature Transition,” Reentrance, and Hydrogen-Bond Dynamics

The temperature-dependent behavior of a solvated oligopeptide, GVG(VPGVG), is investigated. Spectroscopic measurements, thermodynamic measurements, and molecular dynamics simulations find that this elastinlike octapeptide behaves as a two-state system that undergoes an “inverse temperature” folding transition and reentrant unfolding close to the boiling point of water. A molecular picture of these processes is presented, emphasizing changes in the dynamics of hydrogen bonding at the protein/water interface and peptide backbone librational entropy.

Figure 1

(a) CD spectra; (b) Deconvoluted FT-IR absorption spectra; (c) Relative intensities of secondary structure elements obtained from the FT-IR analysis; (d) Thermal expansion coefficient.

Figure 2

Free energy profile along the order parameter coordinate ${\tilde{m}}_1$ at 280 K (●), 330 K (■), and 370 K (◆). For comparison, $\Delta F({\tilde{m}}_i)$ is shown at 370 K for ${\tilde{m}}_2$ (◇), ${\tilde{m}}_3$ (□), and ${\tilde{m}}_4$ (△) in the topmost panel. Plots are offset by $5\mathrm{kJ}/\mathrm{mol}$. Insets: snapshots of representative folded (left: $R_{\mathrm{CN}}\approx 5\AA$) and extended (right: $R_{\mathrm{CN}}\approx 22\AA$) conformations.

Figure 3

Arrhenius plot of rate constants for HB breaking $k_{\mathrm{ps}}$ (●), $k_{\mathrm{bb}}$ (△), $k_{\mathrm{sc}}$ (◇) and HB reformation ${\tilde{k}}_{\mathrm{ps}}$ (■), ${\tilde{k}}_{\mathrm{bb}}$ (▽); note that akin to $\ln (k_{\mathrm{sc}})$, $\ln ({\tilde{k}}_{\mathrm{sc}})$ vs $1/T$ is linear in the entire temperature range with a slope similar to $\ln ({\tilde{k}}_{\mathrm{bb}})$, and thus it is not shown. The symbol sizes cover the error bars, and the lines are linear fits including all temperatures (dashed lines) or separately the regimes above and below 330 K (solid lines).