Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors

Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors

The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) is an immune checkpoint (ICP) overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. To determine important residues for ligand binding, we applied molecular d...

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Bibliographic Details
Main Authors: Suliman Almahmoud, Haizhen A. Zhong
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:International Journal of Molecular Sciences
Subjects:
the PD-1/PD-L1 complex
protein–protein interactions
the PD-L1 protein
docking
ligand–protein interactions
Online Access:https://www.mdpi.com/1422-0067/20/18/4654
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spelling doaj-f8d5f00eec474a759224f05377fb46332020-11-25T01:09:42ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-09-012018465410.3390/ijms20184654ijms20184654Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex InhibitorsSuliman Almahmoud0Haizhen A. Zhong1Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6125, USADepartment of Chemistry, University of Nebraska at Omaha, Omaha, NE 68182, USAThe programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) is an immune checkpoint (ICP) overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. To determine important residues for ligand binding, we applied molecular docking studies to PD-1/PD-L1 complex inhibitors against the PD-L1 protein. Our data revealed that the residues Tyr56, Asp122, and Lys124 play critical roles in ligand binding to the PD-L1 protein and they could be used to design ligands that are active against the PD-1/PD-L1 complex. The formation of H-bonds with Arg125 of the PD-L1 protein may enhance the potency of the PD-1/PD-L1 binding.https://www.mdpi.com/1422-0067/20/18/4654the PD-1/PD-L1 complexprotein–protein interactionsthe PD-L1 proteindockingligand–protein interactions
collection DOAJ
language English
format Article
sources DOAJ
author Suliman Almahmoud
Haizhen A. Zhong
spellingShingle Suliman Almahmoud
Haizhen A. Zhong
Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors
International Journal of Molecular Sciences
the PD-1/PD-L1 complex
protein–protein interactions
the PD-L1 protein
docking
ligand–protein interactions
author_facet Suliman Almahmoud
Haizhen A. Zhong
author_sort Suliman Almahmoud
title Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors
title_short Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors
title_full Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors
title_fullStr Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors
title_full_unstemmed Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors
title_sort molecular modeling studies on the binding mode of the pd-1/pd-l1 complex inhibitors
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2019-09-01
description The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) is an immune checkpoint (ICP) overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. To determine important residues for ligand binding, we applied molecular docking studies to PD-1/PD-L1 complex inhibitors against the PD-L1 protein. Our data revealed that the residues Tyr56, Asp122, and Lys124 play critical roles in ligand binding to the PD-L1 protein and they could be used to design ligands that are active against the PD-1/PD-L1 complex. The formation of H-bonds with Arg125 of the PD-L1 protein may enhance the potency of the PD-1/PD-L1 binding.
topic the PD-1/PD-L1 complex
protein–protein interactions
the PD-L1 protein
docking
ligand–protein interactions
url https://www.mdpi.com/1422-0067/20/18/4654
work_keys_str_mv AT sulimanalmahmoud molecularmodelingstudiesonthebindingmodeofthepd1pdl1complexinhibitors
AT haizhenazhong molecularmodelingstudiesonthebindingmodeofthepd1pdl1complexinhibitors
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