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

Almahmoud, Suliman; Zhong, Haizhen A.

doi:10.3390/ijms20184654

Open AccessArticle

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

by

Suliman Almahmoud

¹ and

Haizhen A. Zhong

^2,*

¹

Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6125, USA

²

Department of Chemistry, University of Nebraska at Omaha, Omaha, NE 68182, USA

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2019, 20(18), 4654; https://doi.org/10.3390/ijms20184654

Submission received: 3 September 2019 / Revised: 15 September 2019 / Accepted: 17 September 2019 / Published: 19 September 2019

(This article belongs to the Section Molecular Pharmacology)

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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: the PD-1/PD-L1 complex; protein–protein interactions; the PD-L1 protein; docking; ligand–protein interactions

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MDPI and ACS Style

Almahmoud, S.; Zhong, H.A. Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors. Int. J. Mol. Sci. 2019, 20, 4654. https://doi.org/10.3390/ijms20184654

AMA Style

Almahmoud S, Zhong HA. Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors. International Journal of Molecular Sciences. 2019; 20(18):4654. https://doi.org/10.3390/ijms20184654

Chicago/Turabian Style

Almahmoud, Suliman, and Haizhen A. Zhong. 2019. "Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors" International Journal of Molecular Sciences 20, no. 18: 4654. https://doi.org/10.3390/ijms20184654

APA Style

Almahmoud, S., & Zhong, H. A. (2019). Molecular Modeling Studies on the Binding Mode of the PD-1/PD-L1 Complex Inhibitors. International Journal of Molecular Sciences, 20(18), 4654. https://doi.org/10.3390/ijms20184654

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

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