Fig. 4: Conformational transition of AE1 between the OF and IF states.
A Schematic of the elevator mechanism for the OF ⇌ IF transition. The definition of the two CVs is shown, where \(z\) and \(\theta\) represent the translational and rotational motions of the TD relative to the SD, respectively. B Cα RMSD of the TM helices during the driven simulations with respect to the target structure in the IF state with SMD denotes the pulling stage. C, D The change of the CVs for the rotation C and translation D during the initial equilibration, driven (SMD), releasing, and final free equilibration simulations, highlighted with different background colors. The CV values of initial and target structures are shown as the dashed red and green lines, respectively. E Refined transition pathways with SMwST for the apo (blue), substrate-bound (orange), and PIP2-removed (green) systems. Each point represents the averaged centers of 8 replicas for 32 swarms. F Free energy profiles computed using BEUS for the apo, substrate-bound, and PIP2-removed systems with same colors as in E. Data are presented as mean ± SD, calculated via bootstrap resampling across 64 windows.
