Figure 5.
Electrostatic and shape complementarity in diamidine binding to PRTM1 and PRMT5: (A) electrostatic potential surface for the binding pocket of PRMT1 with compound 1; (B) electrostatic potential surface for the binding pocket of PRMT5 with compound 1; (C) shape of the binding cavity of PRMT1 (red) with compound 1 (blue); (D) shape of the binding cavity of PRMT5 (red) with compound 1 (blue). The best docking pose obtained from AutoDock for 1 in complex with the hPRMT1 homology model (based on 1F3L(44) and 3SMQ(45)) and X-ray hPRMT5 (4GQB53) was selected for MD simulation. Dominant structures for the hPRMT1·1 and hPRMT5·1 complexes from the last 20 ns of MD trajectory clustering analysis were used for visualization, the same as for Figure 4C,D. The charges of proteins were assigned using PDB2PQR server69 and electrostatic potential was calculated using APBS.68 The electrostatic potential varied from −10KBT/e to +10KBT/e and was depicted using Chimera71 in panels A and B from red to blue, respectively. The ligand in panels A and B is color-coded by AM1BCC charge from red (negative) to blue (positive). The surface was visualized in panels C and D using the program VMD.70