Computational prediction and docking studies of bioactive metabolites from grass-derived endophytic fungi

Endophytic fungi are prolific sources of structurally diverse secondary metabolites with significant agricultural and pharmacological potential. In the present study, bioactive compounds isolated from endophytic fungi (Curvularia tsudae (Ct), Aspergillus chevalieri (ARI 27), Aspergillus stellates (ARI 22), and Hypoxylon sp. (ARI 06) harbored in Cynodon dactylon were analyzed using GC-MS/LC-MS and subjected to computational prediction and molecular docking studies. A total of 26 major metabolites, including phenolics, lactones, alkaloids, coumarins, anthraquinones, and fatty acids, were characterized and evaluated for their drug-likeness, biological activity scores, and binding affinities using chemoinformatic and docking tools. Most compounds adhered to Lipinski's Rule of Five, with favorable logP values and topological polar surface areas indicating good bioavailability. Notably, curvularin, dextramycin, esculetin, and 1,4-dibutyl benzene-1,4-dicarboxylate showed strong docking affinities (- 6.6 to - 9.1 kcal/mol) toward antibacterial and antioxidant targets such as D-alanine-D-alanine ligase, lipoxygenase, 1-heptacosanol and myeloperoxidase. Molecular dynamics simulation was confirmed by normal mode analysis, in which the interactions of the top three protein-ligand pairs were found to be stable, with low eigenvalues of 5.4 × 10^- 5 to 1.57 × 10^- 4; the movement of the residues was regulated, and the group activity of the molecules was observed. PASS predictions confirmed broad-spectrum antibacterial and antifungal activities, with high Pa values (> 0.9) for dextramycin and pyrrolopyrazine derivatives. Structure-activity relationship analysis suggested key interactions mediated by hydroxyl, methoxy, and aromatic groups. This in-silico integration approach revealed the therapeutic potential of grass-derived endophytic fungal metabolites and prioritized potent candidates for future agricultural and pharmacological validation. These findings highlight endophytes as valuable sources of natural compounds for the development of antimicrobial and antioxidant agents.