Discovery of Potential PD-1 and PD-L1 Interaction Inhibitors Using Combined Molecular Modeling Approaches

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dc.contributor.authorUlucan, Özlem
dc.date.accessioned2026-04-04T18:48:31Z
dc.date.available2026-04-04T18:48:31Z
dc.date.issued2025
dc.description.abstractImmune checkpoints are regulators of the immune system that maintain immune homeostasis and prevent autoimmunity. Cancer cells often manipulate immune checkpoint mechanisms to escape anti-tumor immune response by overexpressing the immune checkpoint ligands. Thus, the interactions between the immune checkpoint receptors and ligands attracted attention and were proven to be effective targets in treating cancer. In this study, combining several computational approaches, we discovered small molecules that effectively bind to the ligand Programmed Cell Death Ligand 1 (PD-L1) and have the potential to hamper its interaction with the negative immune checkpoint receptor Programmed Cell Death Protein-1 (PD-1). Different pharmacophore models were constructed using triple and quadruple combinations of the interface residues on PD-1, which were used later for scanning the ZINC15 database. 12714 small molecules were retrieved and virtually screened using molecular docking calculations. The complexes of promising small molecules with PD-L1 were further evaluated using energetic and structural analyses. Our results suggest that the three small molecules ZINC21075815, ZINC70692276, and ZINC64031730 retrieved from the ZINC15 database establish stable and energetically favorable interactions with PD-L1 at the hot region consisting of the residues Tyr 56, Glu 58, Arg 113, Met 115, and Tyr 123. These molecules can be used as a starting point to develop more effective and selective anti-PD-1/PD-L1 inhibitors. © 2025, Adiyaman University. All rights reserved.
dc.description.sponsorshipIstanbul Bilgi University, (AK 085 031)
dc.identifier.doi10.37094/adyujsci.1567604
dc.identifier.endpage34
dc.identifier.issn2147-1630
dc.identifier.issue1
dc.identifier.scopus2-s2.0-105010241837
dc.identifier.scopusqualityQ4
dc.identifier.startpage17
dc.identifier.trdizinid1342488
dc.identifier.urihttps://doi.org/10.37094/adyujsci.1567604
dc.identifier.urihttps://search.trdizin.gov.tr/tr/yayin/detay/1342488
dc.identifier.urihttps://hdl.handle.net/11411/10198
dc.identifier.volume15
dc.indekslendigikaynakScopus
dc.indekslendigikaynakTR-Dizin
dc.language.isoen
dc.publisherAdiyaman University
dc.relation.ispartofAdiyaman University Journal of Science
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_Scopus_20260402
dc.subjectComputer-Aided Drug Design
dc.subjectInhibitory T Cell Receptors, Immunomodulation
dc.subjectMolecular Docking
dc.subjectMolecular Dynamic Simulations
dc.subjectPd-1 Receptor
dc.titleDiscovery of Potential PD-1 and PD-L1 Interaction Inhibitors Using Combined Molecular Modeling Approaches
dc.typeArticle

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