Fig. 4. The synergistic activation mechanism of AT₁ receptor.

A–C The comparison of representative inactive (A, blue), intermediate (B, cyan), and active (C, orange) structures. Zoom-in views of key structures are depicted on the right of (A), (B), and (C). Top left: the breaking of hydrophobic lock during activation. Top right: the activation renders the approach of Y^7.53 and Y^5.58. Bottom left: polar interaction on the position of common ionic lock is broken on the process of activation. Bottom right: F^6.44 and F^6.45 ratchet past F^5.51 with the outward movement of TM6. Distances between atoms are shown in dashed yellow lines. Dynamic variations of these activation properties during a representative simulation trajectory are shown in (D) for the distance between the guanidine carbon atom of R^3.50 and the Cγ atom of N^6.30 (red), (E) for the area of the triangle composed of the Cγ atom of L^3.43, the Cβ atom of V^6.41, and the Cβ atom of I^6.40 (blue), and (F) for the angle among the centroids of the benzene ring of F^5.51, F^6.44, and F^6.45 (yellow).