Structural Insights of PD-1/PD-L1 Axis: An In silico Approach

Background: Interaction of PD-1 protein (present on immune T-cell) with its ligand PD-L1 (over-expressed on cancerous cell) makes the cancerous cell survive and thrive. The association of PD-1/PD-L1 represents a classical protein-protein interaction (PPI), where receptor and ligand binding through a large flat surface. Blocking the PD-1/PDL-1 complex formation can restore the normal immune mechanism, thereby destroying cancerous cells. However, the PD-1/PDL1 interactions are only partially characterized. Objective: We aim to comprehend the time-dependent behavior of PD-1 upon its binding with PD-L1. Methods: The current work focuses on a molecular dynamics simulation (MDs) simulation study of apo and ligand bound PD-1. Results: Our simulation reveals the flexible nature of the PD-1, both in apo and bound form. Moreover, the current study also differentiates the type of strong and weak interactions which could be targeted to overcome the complex formation. Conclusion: The current article could provide a valuable structural insight about the target protein (PD-1) and its ligand (PD-L1) which could open new opportunities in developing small molecule inhibitors (SMIs) targeting either PD-1 or PD-L1.