Molecular dynamics insights into the redox effects on PD-1/PD-L1 and PD-1/PD-L2 interactions

The PD-1/PD-L1/PD-L2 immune checkpoint plays a critical role in regulating immune responses, and its dysfunction is implicated in immune evasion by cancer cells. Cold atmospheric plasma (CAP) has emerged as a promising cancer therapeutic modality with the potential to modulate immune checkpoints. This study employs molecular dynamics (MD) simulations to investigate the impact of CAP-induced oxidation on the interactions between PD-1 and its ligands, PD-L1 and PD-L2. We simulated the PD-1/PD-L1 and PD-1/PD-L2 complexes under different oxidation levels by oxidizing vulnerable residues within the interaction site of the ligands. MD simulations combined with enhanced sampling methods revealed that increasing oxidation levels leads to weaken the binding affinity between PD-1 and both PD-L1/PD-L2. These findings suggest that CAP may offer a novel strategy for enhancing anti-tumor immunity. This computational study provides valuable insights into the molecular mechanisms underlying CAP's effects on immune regulation and highlights its potential for cancer immunotherapy.