Abstract
Cancer is a major global health burden, causing significant economic losses and premature deaths worldwide. Maintenance of telomeric repeats by telomerase makes the cancer cells immortal. Non-nucleoside mushroom metabolites were screened for their ability to stabilize RG4 structures, making telomeres inaccessible to telomerase and inducing telomere shortening in cancer cells. Selected mushroom metabolites, namely, Sterenin M, Melleolide K, and Zhankuic Acid A were docked with RG4 using the AutoDock Vina and evaluated for non-covalent interactions. These compounds were found to have strong binding affinity and manifested a set of molecular interactions with RG4. To assess the stability of complexes, state-of-the-art molecular dynamics simulations were carried out using the GROMACS 2018.7 software suite with the AMBER99SB-ILDN force field on 250 nanoseconds. Molecular docking and MD simulations revealed the strong interaction patterns between RG4 and the selected metabolites at the atomic level followed by binding free energy calculations. The results suggest that all three metabolites have the potential to be developed into therapeutic agents for cancer treatment. Further in vitro and in vivo studies are needed to assess these compounds' toxicity, efficacy, and dosage.