Fig. 6: The case of the HIV-1 TAR.

A 2D structure of the HIV-1 TAR. The two stem regions are indicated in light gray; the bulge (residues 23–25) and the apical loop (residues 30–35) in black. B–C Representative RNA clusters determined by the SHAMAN simulations initiated from the holo-like (B) and apo (C) conformations. SHAMAPs are visualized as solid surfaces with the color code defined in Tab. S7 and S8. The RNA state labeled as “conf e” in panel C is represented as a gray surface to highlight the orange region explored by ACEY (red density) and MAMY (rose density). This area corresponds to the cryptic binding site identified by Davidson et al. ⁵⁸. D, E Representative RNA conformations and SHAMAPs with best overlap with the experimental binding sites found in the simulations initiated from the holo-like (D) and apo (E) conformations. In the insets, SHAMAPs that best identified the 5 ligands present in our validation set (Tab. S4): clockwise from top left, ARG in PDB 1arj, PMZ in PDB 1lvj, P13 in PDB 1uts, P12 in PDB 1uui, MV2003 in PDB 2l8h. F 2D structures of the probes that successfully identified the experimental binding sites. The brown and cyan dashed circles indicate the successful probes in the holo-like and apo simulations, respectively.