Computational Study of the Binding Modes of Caffeine to the Adenosine A<sub>2A</sub> Receptor

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dc.contributor.authorLiu, Yuli
dc.contributor.authorBurger, Steven K.
dc.contributor.authorAyers, Paul W.
dc.contributor.authorVoehringer-Martinez, Esteban
dc.date.accessioned2025-01-21T00:00:06Z
dc.date.available2025-01-21T00:00:06Z
dc.date.issued2011
dc.description.abstractUsing the recently solved crystal structure of the human adenosine A(2A) receptor, we applied MM/PBSA to compare the binding modes of caffeine with those of the high-affinity selective antagonist ZM241385. MD simulations were performed in the environment of the lipid membrane bilayer. Four low-energy binding modes of caffeine-A(2A) were found, all of which had similar energies. Assuming an equal contribution of each binding mode of caffeine, the computed binding free energy difference between caffeine and ZM241385 is -2.4 kcal/mol, which compares favorably with the experimental value, -3.6 kcal/mol. The configurational entropy contribution of -0.9 kcal/mol from multiple binding modes of caffeine helps explain how a small molecule like caffeine can compete with a significantly larger molecule, ZM241385, which can form many more interactions with the receptor. We also performed residue-wise energy decomposition and found that Phe168, Leu249, and Ile274 contribute most significantly to the binding modes of caffeine and ZM241385.
dc.fuente.origenWOS
dc.identifier.doi10.1021/jp2022049
dc.identifier.eissn1520-5207
dc.identifier.issn1520-6106
dc.identifier.urihttps://doi.org/10.1021/jp2022049
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95324
dc.identifier.wosidWOS:000297195400011
dc.issue.numero47
dc.language.isoen
dc.pagina.final13890
dc.pagina.inicio13880
dc.revistaJournal of physical chemistry b
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleComputational Study of the Binding Modes of Caffeine to the Adenosine A<sub>2A</sub> Receptor
dc.typeartículo
dc.volumen115
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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