Fig. 3.
Free-energy landscapes along PP1 position and orientation. (A) Polar angles, θ (P2-P1-L1) and φ (P3-P2-P1-L1) designating PP1 position (Left) and Euler angles, α (P1-L1-L2), β (P2-P1-L1-L2), and γ (P1-L1-L2-L3), designating PP1 orientation (Right). (B) Free-energy landscapes at 310 K along the PP1-Src distance (ξ) and polar angles (θ and φ) for the gREST/REUS simulation. (C) Similar landscapes as in B for Euler angles (α, β, and γ). Positions of representative structures in each state from the k-means clustering analysis are marked on the landscapes (white: bound state; gray: intermediate; black: encounter state). The pathway to the canonical binding pose (Ezz → Bzz) is indicated by the gray arrow line. The plausible parallel binding pathways to multiple poses are indicated by solid and dotted frames.