2D-PMF with respect to A-loop opening and αC-helix rotation. All free energies are in the unit of kcal/mol, and all distances are in the unit of Å. (a) assembled SH2/SH3, (b) catalytic domain only, used as a model for the SH2/SH3 dissociated state, (c) N-linker constrained to the assembled state, and (d) re-assembled SH2/SH3. Each subplot is accompanied by a visual of the characteristic in-active and active state for the specific system. The surfaces of the KD, SH2 and SH3 are shown in blue, green and yellow respectively. The linker, A-loop and phosphorylated C-terminal tail are shown when present.