Exploring inhibitory components of Hedyotis diffusa on androgen receptor through molecular docking and molecular dynamics simulations

To explore the effective ingredients and mechanisms of action in Hedyotis diffusa (HD) that have inhibitory effects on androgen receptors (AR) using molecular docking and molecular dynamics simulations (MDS). The effective ingredients of HD were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database and literatures. All components were docked with AR using Libdock. The receptor ligand interaction between the optimal ligand and AR were analyzed. Two simulation systems, namely I and II, containing AR and testosterone propionates (TP) were constructed, which System II contained the optimal ligand. The duration of the MDS was set to 300 ns. The distance between TP and AR peripheral active sites, root mean square deviation of ligand and receptor, receptor radius of gyration, distance between ligand center and binding site center, and ligand receptor binding energy were analyzed. 37 components of HD were collected, and the optimal ligand was MOL001656. MOL001656 forms hydrogen bonds with residues LEU48, PHE108, GLN55, LEU45, and ASN49 of AR. MDS have found that binding of TP to AR active sites can be observed in System I. The root mean square deviation of AR and MOL001656 both tended to stabilize in System II, with no significant fluctuations in the radius of gyration of AR and no significant fluctuations in the distance between ligand and binding cavity, indicating that the receptor ligand structure is relatively stable and their binding is relatively stable. The binding energy between AR and MOL001656 was -29.33 +/- 3.84 kcal/mol. HD contains multiple effective ingredients that may have inhibitory AR activity. MOL001656 can occupy binding sites, thereby may exerting AR inhibitory effects.