Fig. 3.

PAI-1 energy landscape shows pronounced minima for the prelatent and latent states. (A) Potential energy evaluated along the dominant pathways for PAI-1 WT (black curve), the PAI-1 variants (red and blue curves), and A1AT (brown curve) as a function of the total Euclidean distance covered by the C_α atoms during the latency transition. The structure in the upper right corner corresponds to the PAI-1 prelatent state. To resolve the energy landscapes better, the plotted potential energies were averaged over 15 consecutive frames in the DRP trajectories. The Euclidean distance is defined as $l={\displaystyle {\sum }_{i=1}^{Ns}\sqrt{{\displaystyle {\sum }_{k=1}^{N_{C_{\alpha }}}{\left({\overrightarrow{x}}_{i+1}^k\mathrm{-}{\overrightarrow{x}}_i^k\right)}^2}}},$ where Ns is the number of frames in the dominant trajectory, N_Cα is the number of residues in the protein, and ${\overrightarrow{x}}_i^k$ is the position of the kth C_α atom in the ith frame. U_pot, potential energy. (B) rmsd to the latent state as a function of the number of rMD steps for all three PAI-1 variants. The prelatent state is revealed by a clear plateau in all three curves. (C) Mutations and active t_1/2s for the PAI-1 variants.