Investigation Of The Binding Affinities Of Natural Compounds To Specific Protein Targets Through Docking

Abstract

Natural products have long served as valuable sources of bioactive molecules, many of which exhibit potent therapeutic properties with minimal adverse effects. Development of drug discovery processes that are computational; has seen the molecular docking becoming an indispensable method for the rapid prediction of protein-ligand interactions and the selection of good natural candidates for further studies. In this paper, we looked at how well and in what way the natural polyphenolic compound **ellagic acid (EA)** interacted with Poly (ADP-ribose) polymerase 10 (PARP10), a cancer-causing enzyme mono-ADP-ribosyltransferase that is very much involved in the tolerating of replication stress, inflammatory processes, and tumor growth. The goal was to find out if EA is a PARP10-inhibitor with potencies corresponding to anticancer drugs.

Molecular docking studies were conducted using AutoDock Vina 1.2.7, after very careful preparation of the protein and ligand done by UCSF Chimera, Chem3D, and AutoDockTools. Layout of the required grid parameters was done using AutoGridFR to have precise identification of the catalytically active binding region. A total of ten docking modes were subjected to exploration with a very high degree of exhaustiveness to make sure that the sampling of the poses was correctly done. The analysis of the post-docking results was done using the BIOVIA Discovery Studio Visualizer where characterization of the hydrogen bonding, hydrophobic contacts and π–π interactions was done.

EA showed a very strong binding affinity of –9.554 kcal/mol, which was greater than that of the re-docked co-crystallized inhibitor Veliparib (–8.5 kcal/mol) and this fact pointed out the validity of both the protocol and the possible superiority of EA as a binder.Interaction mapping revealed stabilizing hydrogen bonds with Tyr919 and Ala911, along with π–π stacking involving Tyr932 and His887, highlighting excellent structural complementarity within the PARP10 catalytic site. Overall, the results indicate that ellagic acid may act as a promising natural inhibitor of PARP10 with potential implications in cancer therapy. While docking provides a strong theoretical foundation, further validation through molecular dynamics simulations, enzymatic inhibition assays, and cellular studies is required to confirm its biological relevance and therapeutic potential.