Identification of Potential Inhibitors for Poly(ADP‐ribose) Polymerase‐10 (PARP10): Virtual Screening, Molecular Docking, and Molecular Dynamics Simulations

Abstract Poly(ADP‐ribose) polymerase‐10 (PARP10) is a critical enzyme involved in DNA damage repair. Its function in cellular repair mechanisms has been implicated in the development of chemoresistance and radioresistance in cancer cells. Consequently, PARP10 inhibition represents a promising, albeit challenging, and therapeutic target for various cancer types. This study aims to discover new PARP10 potential inhibitors via a hybrid of in silico approaches. Initially, pharmacophore‐based virtual screening was conducted on the ZINC and NCI databases. The resulting compounds were subsequently subjected to molecular docking studies to identify potential new PARP10 inhibitors. Subsequently, classical molecular dynamics (MD) simulations were conducted to evaluate and compare the dynamic behavior of the selected ligand, veliparib, and OUL35, a selective PARP10 inhibitor. Ultimately, compound ZINC20906412 was found as a potential lead compound based on its docking score and favorable interactions within the PARP10 active site. This compound may offer therapeutic potential for cancer treatment.