domain. Interestingly, the LNR-B module (residue ID 43–74) appears to dynamically uncoupled from both LNR-A (residue ID 1–32) and LNR-C (residue ID 81–114), possibly due to long linkers between three LNR modules. (TIF) Movie S1 A movie of a representative force unfolding simulation. The Notch1 NRR is represented using the same scheme as in Fig. 4 of the main text. Specifically, the LNR-A, LNR-B and LNR-C modules are colored in blue, green and red, respectively, and the HDN and HDC subunits of the HD domain in cyan and purple, respectively. The N- and C-terminal Ca beads where the external force is exerted are shown in black spheres. The S2 site is marked using purple spheres. N. B. while the protein is allow to freely diffuse and rotate during the pulling simulations, References 1. Artavanis-Tsakonas S, Muskavitch MA (2010) Notch: the past, the present, and the future. Curr Top Dev Biol 92: 1–29. 2. 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