Strategic Identification of Anti-Cancer Compounds Targeting PARP15 in DNA Repair Pathways for Enhanced Therapeutic Efficacy

Abstract

Cancer is a significant worldwide health concern that requires effective therapies. Addressing this critical issue necessitates innovative treatment strategies concentrating on the fundamental causes of cancer progression. The PARP15 protein is essential in cancer progression by facilitating DNA repair pathways, making it a promising target for anti-cancer therapies. This investigation relies on computational strategies, including virtual screening and molecular dynamics simulations, to identify potential inhibitors of PARP15 target protein. Three potential compounds (26646684, 104224077, and 17505556) with notable binding affinities and interaction patterns were selected for further investigation. Compound 17505556 shows significant interactions, suggesting more stable conformation throughout the simulation against the target protein. Compound 17505556 exhibited the highest binding free energy (-34.07 kcal/mol), significantly outperforming the reference inhibitor I4X (-26.70 kcal/mol). This strong binding affinity suggests that 17505556 forms stable and sustained interactions with PARP15, making it the most promising inhibitor among those studied. Other compounds, 26646684 (-28.92 kcal/mol) and 104224077 (-26.83 kcal/mol), also demonstrated favorable binding energies, indicating their potential as viable inhibitors. The overall result of the investigation suggests the compound 17505556 as a possible drug candidate for the inhibition of DNA repair protein, offering novel avenues for developing an anti-cancer drug candidate.