Figure 2.

Round-trip time analysis of folding simulations (color online). (A) Extension trajectories for folding of a hairpin with the given energy landscape (inset) were simulated by assuming a constant force applied to the end of the hairpin, either directly or via a 400-nm radius bead attached to the hairpin by a handle of stiffness k. (B) A simulated extension trajectory in the absence of beads and handles is shown. Dashed lines indicate the locations of the unfolded (x_u) and folded (x_f) states. (C) The average round-trip times calculated from the trajectory in (B) with respect to reference points x_f (black) and x_u (red, inverted for ease of comparison) agree well. (D) The diffusivity profiles calculated from the round-trip times in (C) agree well for both choices of reference point (black: x_f, red: x_u), and recover the constant diffusion coefficient imposed in the simulation (cyan) except near the reference points. (E) After repeating the analysis for simulations including a stiff (black/gray: k = 1 pN/nm) or compliant (red/pink: k = 0.2 pN/nm) handle, the results for the two choices of reference point (black/red: x_f, gray/pink: x_u) are somewhat similar for the stiff handle but differ substantially for the compliant handle. The diffusivity profile is degraded only slightly for the stiff handle compared to the no-handle simulation but significantly for the compliant handle. (F) When the folding is simulated without handles while imposing a spatially varying diffusivity (dot-dashed line), the diffusivity profile is again recovered reasonably well for both reference points (black: x_f, red: x_u). Error bars represent SE. To see this figure in color, go online.