Structure-based screening and identification of a novel Aurora-A-targeting peptide with antiproliferative activity against prostate cancer cells.

Aurora-A is a potential therapeutic target in prostate cancer. In this study, virtual screening identified four Aurora-A-targeting peptides, among which Peptide-1 showed the most favourable profile. Molecular docking and MST assays demonstrated that Peptide-1 had the lowest predicted binding free energy and the strongest binding affinity towards Aurora-A (Kd = 0.72 ± 0.04 μM). MD simulation, MM/PBSA, and free-energy landscape analyses indicated that the Aurora-A-Peptide-1 complex was conformationally stable and mainly driven by electrostatic interactions. MTT assays showed that Peptide-1 inhibited the proliferation of PC3, DU145, and NCI-H660 cells, with weaker activity in RWPE-1 cells. Aurora-A knockdown reduced cellular sensitivity to Peptide-1, supporting its target-dependent activity. qRT-PCR further showed increased p53 and p21 mRNA expression after Peptide-1 treatment in PC3/p53WT cells. These findings suggest that Peptide-1 may act as an Aurora-A-targeting peptide with antiproliferative activity in prostate cancer cells.