title: In Silico Investigation of Potential PARP-1 Inhibitors from Traditional Chinese Medicine.
abstract: Poly(ADP-ribose) polymerases (PARPs) are nuclear enzymes which catalyze the poly-ADP-ribosylation involved in gene transcription, DNA damage repair, and cell-death signaling. As PARP-1 protein contains a DNA-binding domain, which can bind to DNA strand breaks and repair the damaged DNA over a low basal level, the inhibitors of poly(ADP-ribose) polymerase 1 (PARP-1) have been indicated as the agents treated for cancer. This study employed the compounds from TCM Database@Taiwan to identify the potential PARP-1 inhibitors from the vast repertoire of TCM compounds. The binding affinities of the potential TCM compounds were also predicted utilized several distinct scoring functions. Molecular dynamics simulations were performed to optimize the result of docking simulation and analyze the stability of interactions between protein and ligand. The top TCM candidates, isopraeroside IV, picrasidine M, and aurantiamide acetate, had higher potent binding affinities than control, A927929. They have stable H-bonds with residues Gly202 and, Ser243 as A927929 and stable H-bonds with residues Asp105, Tyr228, and His248 in the other side of the binding domain, which may strengthen and stabilize ligand inside the binding domain of PARP-1 protein. Hence, we propose isopraeroside IV and aurantiamide acetate as potential lead compounds for further study in drug development process with the PARP-1 protein.
authors.affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan.
authors.forename: Kuan-Chung
authors.identifier: 0000-0003-0223-1577
authors.initials: KC
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine-Acupuncture Science, China Medical University, Taichung 40402, Taiwan.
authors.forename: Mao-Feng
authors.identifier: 0000-0003-1465-0330
authors.initials: MF
authors.lastname: Sun
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Calvin Yu-Chian
authors.identifier: 0000-0003-3306-250X
authors.initials: CY
authors.lastname: Chen