Ligand-Dependent Sodium Ion Dynamics within the A_2A Adenosine Receptor: A Molecular Dynamics Study

Journal Article · Wed Sep 04 00:00:00 UTC 2019 · Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry

DOI:https://doi.org/10.1021/acs.jpcb.9b04474· OSTI ID:1561656

Hu, Xiaohu ^[1]; Smith, Micholas Dean ^[2]; Humphreys, Bailey M. ^[2]; Green, Adam T. ^[2]; Parks, Jerry M. ^[3]; Baudry, Jerome Y. ^[4]; Smith, Jeremy C. ^[2]

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1. Univ. of Tennessee, Knoxville, TN (United States); Icahn School of Medicine at Mount Sinai, New York, NY (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
2. Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
3. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
4. Univ. of Alabama, Huntsville, AL (United States)

Sodium ions have long been known to reduce the binding of agonists in many class-A GPCRs while having little effect on antagonist binding. In this study, using long-time scale classical all-atom molecular dynamics simulations, we explore, in atomic detail, the motion of sodium ions within the ligand-binding pocket of the A_2A adenosine receptor (A2A-AR) both in the presence and absence of ligands and in the active and inactive state. We identify novel secondary ion binding sites within the pocket and find that the types of ion motions within the pocket are highly dependent on the presence and type of ligand within the pocket. Finally, our results provide a first step toward developing a molecular understanding of the impact of sodium ions on class-A GPCRs.

• Research Organization: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: USDOE
• Grant/Contract Number: AC05-00OR22725
• OSTI ID: 1561656
• Journal Information: Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry, Journal Name: Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry Journal Issue: 38 Vol. 123; ISSN 1520-6106
• Publisher: American Chemical Society
• Country of Publication: United States
• Language: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
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