Fig. 2: Molecular dynamics simulations of EPI-002 and EPI-7170 binding the disordered Tau-5R2_R3 region of the androgen receptor N-terminal transactivation domain.
A Per-residue contact probabilities were observed between Tau-5R2_R3 and EPI-002 (blue) and EPI-7170 (orange) in REST2 MD simulations. Contacts are defined as occurring in frames where any non-hydrogen ligand atom is within 6.0 Å of a non-hydrogen protein atom. Contact probabilities are reported as mean values ± statistical error estimates from blocking. B Average Cα-atom radius of gyration (Rg) of Tau-5R2_R3 conformations as a function of the minimum number of distinct residue contacts formed in MD simulations. Values are presented as means and error bars reflect the variance of Rg values observed in each subset of Tau-5R2_R3 conformations. Diamonds reflect the average radius of gyration of Tau-5R2_R3 conformations in frames with no protein-ligand contacts in simulations in the presence of ligands. C The probability that a pair of residues in Tau-5R2_R3 simultaneously form ligand contacts in the EPI-002:Tau-5R2_R3 and EPI-710:Tau-5R2_R3 bound ensembles. D Chemical structures of EPI-002 and EPI-7170 and illustrative MD Snapshots of Tau-5R2_R3 interacting with ligands. The R2 and R3 helices of Tau-5R2_R3 are colored red and blue, respectively. KD values observed in MD simulations were calculated by defining the bound population (Pb) as the fraction frames with at least one ligand contact, and the reported statistical error estimates were obtained from a blocking analysis. Source data are provided as a Source Data file.
