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Updated: Jun 17, 2025
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
In silico exploration of PD-L1 binding compounds: Structure-based virtual screening, molecular docking, and MD
Abdullah Alanzi1, Ashaimaa Y Moussa2, Ramzi A Mothana1
1Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Abstract:
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.
Insights
Researchers identified potential new drug compounds targeting Programmed Death-Ligand 1 (PD-L1) to enhance cancer immunotherapy. These compounds show promise for inhibiting PD-L1 activity in early in vitro studies.
Area of Science:
- Immunology
- Computational Chemistry
- Pharmacology
Background:
- Programmed death-ligand 1 (PD-L1) is a transmembrane protein crucial for immune system regulation.
- Overexpression of PD-L1 in cancers enables tumor cells to evade immune detection.
- Inhibiting PD-L1 is a promising therapeutic strategy in cancer immunology.
Purpose of the Study:
- To identify novel small molecules for PD-L1 inhibition using structure-based virtual screening.
- To evaluate the binding affinity and stability of potential drug candidates.
- To assess the drug-likeness of identified compounds through ADMET analysis.
Main Methods:
- Structure-based virtual screening of drug libraries against PD-L1.
- Molecular docking to determine optimal binding poses and affinities.
- Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis.
- 200 ns molecular dynamics simulations for top compounds.
Main Results:
- Ten compounds exhibited high binding affinities to PD-L1, ranging from -10.734 to -10.398 kcal/mol.
- Selected compounds demonstrated favorable ADMET properties.
- Molecular dynamics simulations confirmed binding stability without significant conformational changes to PD-L1.
Conclusions:
- The identified compounds are potential lead candidates for PD-L1 inhibition.
- These findings support further in vitro investigation for developing novel cancer immunotherapies.
- The study highlights the utility of computational methods in drug discovery for PD-L1 targeted therapies.
