In silico exploration of PD-L1 binding compounds: Structure-based virtual screening, molecular docking, and MD simulation

Programmed death-ligand 1 (PD-L1), a transmembrane protein, is associated with the regulation of immune system. It frequently has overexpression in various cancers, allowing tumor cells to avoid immune detection. PD-L1 inhibition has risen as a potential strategy in the field of therapeutic immunology for cancer. In the current study, structure-based virtual screening of drug libraries was conducted and then the screened hits were docked to the active residues of PD-L1 to select the optimal binding poses. The top ten compounds with binding affinities ranging from -10.734 to -10.398 kcal/mol were selected for further analysis. The ADMET analysis of selected compounds showed the compounds meet the criteria of ADMET properties. Further, the conformational changes and binding stability of the top two compounds was analyzed by conducting 200 ns simulation and it was observed that the hits did not exert conformational changes to the protein structure. All the results suggest that the chosen hits can be considered as lead compounds for the inhibition of biological activity of PD-L1 in in vitro studies.