Molecular Dynamics and Virtual Screening Analysis of Lanosterol Derivatives from Ganoderma Medicinal Mushrooms (Agaricomycetes) as Selective Ligands of Human Androgen Receptor

Male sex hormones such as testosterone and dihydrotestosterone play important roles in several physiological and pathological processes. The biological activities of the aforementioned metabolites are mediated by the multidomain androgen receptor (AR), which is therefore a well-studied drug target. Ganoderma mushroom lanostanoid extracts have previously been shown to exert antiandrogenic activity; therefore, this work aims to identify which lanostane derivatives might act as selective ligands for AR. Because protein flexibility is of paramount importance for ligand binding, different conformations of AR were sampled to account for binding modes within a ligand binding site, then subjected to virtual screening against a metabolite library. Fifteen Ganoderma lanostanoids were selected as AR ligands, according to their calculated binding affinity to this nuclear receptor. The results show the relevance of certain structural and chemical aspects of our ligands, such as the presence of a ketonic group on C-3, which influences the process through which they bind to AR.