Fig. 1. (a) Time evolution of the RMSD of the Trp-cage to its native structure, the slow variables B₁ and B₂ obtained in the TM. Red line is time-window-smoothed one (Δ t = 200 ns). (b) Eigenvalue of the variance–covariance matrix of the trajectory-mapped points. The inset is the contribution of each basis function to the slow variables B₁ and B₂. (c) The free-energy landscape (in units of k_BT) in the slow-variable space (B₁, B₂).

Fig. 2. Time-ordered similarity matrix of the MD trajectory. The similarity between two samples C(t₂, t₁) = B(t₂) ⋅ B(t₁). (b) The time-rearranged similarity matrix, suggesting three metastable states. (c) Kinetic transition network. Numbers near the arrows are the corresponding transition rates. The population of each state in the 208-μs MD trajectory is listed in bracket (which approaches to the equilibrium one, in consistent with the fact the folding and unfolding transitions occur more than ten times during the MD simulation). Residue TRP6 and PRO17 are shown in blue, GLY11 in red.