Structural Analysis and Functional Prediction of the Target Protein AR of Medicagol, an Active Component of Millettia reticulata

To investigate the interaction mechanism between the steroidal active component Medicagol from Millettia reticulata and the androgen receptor (AR) using bioinformatics, and to explore its potential therapeutic effects. Active components of Millettia reticulata were screened using the TCMSP database. Multiple sequence alignment and phylogenetic tree construction of AR were performed with MEGA X (10.0.5). The primary structure was analyzed using ProtParam, hydrophobicity predicted by Protscale, and conserved domains identified via Prosite. Secondary structure was analyzed using NPS@SOPMA, while tertiary structure was predicted by homology modeling from the RCSB PDB database. Subcellular localization was predicted using DeepLoc-2.0, and molecular docking was performed with SwissDock to verify the interaction between Medicagol and AR. The AR protein consists of 920 amino acids with a molecular weight of 99.19 kDa and a theoretical isoelectric point of 6.00, classifying it as a hydrophilic and unstable protein. Its secondary structure is predominantly random coil (74.13%), with the presence of a nuclear receptor ligand-binding domain (NR LBD) and C4-type zinc finger motifs. Medicagol anchors into the AR ligand-binding pocket through hydrophobic interactions and hydrogen bonds, with key residues including Pro, Glu, Lys, and Ala. AR is highly conserved among primates, clustering closely with Pongo abelii and Gorilla gorilla gorilla. Molecular docking confirmed that Medicagol forms a stable complex with AR. This study elucidates the molecular binding mechanism of Medicagol with AR, providing theoretical support for the development of AR-targeted immunoregulatory drugs and the precise utilization of medicinal-food homologous resources.