Figure 2.

Schematic templates of EPAC1 used for ensemble generation in EOM. The dashed-lines denote flexible regions used to generate the ensembles. The NTD: “N” is in yellow; the regulatory DEP and CNBD domains: “B” are green; and the catalytic RA, REM, and GEF domains: “GEF” in blue. (a) The “Apo” model based on the apo-EPAC1 homology model with a tethered (aa 80–94) NTD. In addition, an IDP model of the NTD used a randomly generated chain-of-beads for both the linker and the NTD. (b) The flexible (aa 348–351) Hinge and switchboard “SB” model. This model produced four unique EPAC1_extended models with similar hinge angles. (c) These four models of the Hinge angle were used in the “Hinge” ensembles. The tethered (aa 80–94) NTD distribution is more compact than the “SB” distribution, which is under-sampled due to its high flexibility. (d) The “Camp” ternary-like model based on the cAMP-bound EPAC1 homology model. The Hinge and switchboard are locked and the NTD is tethered by a flexible linker (aa 80–94). For each EPAC1 EOM template, 10,000 unique models were generated.