Molecular modeling studies on the binding mode of the PD-1/PD-L1 complex inhibitors

Suliman Almahmoud; Haizhen A. Zhong

doi:10.3390/ijms20184654

Molecular modeling studies on the binding mode of the PD-1/PD-L1 complex inhibitors

Suliman Almahmoud, Haizhen A. Zhong

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

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.

Original language	English (US)
Article number	4654
Journal	International journal of molecular sciences
Volume	20
Issue number	18
DOIs	https://doi.org/10.3390/ijms20184654
State	Published - Sep 2 2019

Keywords

Docking
Ligand-protein interactions
Protein-protein interactions
The PD-1/PD-L1 complex
The PD-L1 protein

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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10.3390/ijms20184654

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title = "Molecular modeling studies on the binding mode of the PD-1/PD-L1 complex inhibitors",

abstract = "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.",

keywords = "Docking, Ligand-protein interactions, Protein-protein interactions, The PD-1/PD-L1 complex, The PD-L1 protein",

author = "Suliman Almahmoud and Zhong, {Haizhen A.}",

note = "Funding Information: Acknowledgments: Suliman Almahmoud acknowledges The Saudi Arabian Cultural Mission (SACM) for financial support. H.A.Z. is in debt to the generous support in the complimentary use of the MT-based free energy calculation method from Kenneth Merz Jr.{\textquoteright}s group at Michigan State University, East Lansing, Michigan, USA. S.A. and H.A.Z. thank the kind support of Jonathan Vennerstrom at the College of Pharmacy, University of Nebraska Medical Center for valuable suggestions on this manuscript. H.A.Z. is in debt to the Library of the University of Nebraska at Omaha for the Open-Access Fund. Funding Information: Funding: This work was financially supported by the University of Nebraska at Omaha. Suliman Almahmoud was supported by the Ministry of Education Scholarship, Qassim University (Buraydah, Saudi Arabia). Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

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doi = "10.3390/ijms20184654",

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volume = "20",

journal = "International Journal of Molecular Sciences",

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N2 - 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.

AB - 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.

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Molecular modeling studies on the binding mode of the PD-1/PD-L1 complex inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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