Fig. 4.
Atomic details of the process of cohesin stretching obtained through all-atom molecular dynamics simulations. Free MD trajectories and steered MD of cohesins or I27 are shown in Movie S1 and Movie S2 using both the GBSA (18, 37–40) and the exW (19) approximations. (A) Steered MD simulations of cohesin stretching by using the GBSA approximation. Different snapshots at every 200 ps were taken as the starting point of several unfolding trajectories. The averages of the force-distance traces are shown. This approximation reproduces the experimental mechanical hierarchy and the unfolding forces are in the same order of magnitude as experimental data (FI27 = 370 ± 80 pN; Fc7A = 710 ± 120 pN; Fc1C = 630 ± 70 pN; and Fc2A = 470 ± 80 pN). (B) Steered MD simulations of cohesin stretching using the exW approximation. As previously reported (19), this approximation yields unfolding forces one order-of-magnitude larger than the experimental results. Also, the relative order of the mechanical stabilities for the cohesin modules under study is less well reproduced than with the GBSA approximation at the same pulling speed (FI27 = 910 ± 50 pN; Fc7A = 1360 ± 50 pN; Fc1C = 1610 ± 30 pN; and Fc2A = 860 ± 50 pN; Table S1). In addition, 2 lower speeds were used, separated by an order of magnitude. The 3 different pulling speeds are represented from left to right (1, 0.1, and 0.01 Å/ps, respectively). (C) Histograms of the unfolding force peaks from several trajectories obtained through the GBSA approximation at 1 Å/ps are shown. (D) One trajectory obtained by the exW approximation at 0.01 Å/ps is presented.