TY - JOUR
T1 - Exploring the recognition pathway at the human A2A adenosine receptor of the endogenous agonist adenosine using supervised molecular dynamics simulations
AU - Sabbadin, Davide
AU - Ciancetta, Antonella
AU - Deganutti, Giuseppe
AU - Cuzzolin, Alberto
AU - Moro, Stefano
PY - 2015/4/20
Y1 - 2015/4/20
N2 - Adenosine is a naturally occurring purine nucleoside that exerts a variety of important biological functions through the activation of four G protein-coupled receptor (GPCR) isoforms, namely the A1, A2A, A2B and A3 adenosine receptors (ARs). Recently, the X-ray structure of adenosine-bound hA2A AR has been solved, thus providing precious structural details on receptor recognition and activation mechanisms. To date, however, little is still known about the possible recognition pathway the endogenous agonist might go through while approaching the hA2A AR from the extracellular environment. In the present work, we report the adenosine-hA2A AR recognition pathway through the analysis of a series of Supervised Molecular Dynamics (SuMD) trajectories. Interestingly, a possible energetically stable meta-binding site has been detected and characterized.
AB - Adenosine is a naturally occurring purine nucleoside that exerts a variety of important biological functions through the activation of four G protein-coupled receptor (GPCR) isoforms, namely the A1, A2A, A2B and A3 adenosine receptors (ARs). Recently, the X-ray structure of adenosine-bound hA2A AR has been solved, thus providing precious structural details on receptor recognition and activation mechanisms. To date, however, little is still known about the possible recognition pathway the endogenous agonist might go through while approaching the hA2A AR from the extracellular environment. In the present work, we report the adenosine-hA2A AR recognition pathway through the analysis of a series of Supervised Molecular Dynamics (SuMD) trajectories. Interestingly, a possible energetically stable meta-binding site has been detected and characterized.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84935834475&partnerID=MN8TOARS
U2 - 10.1039/c5md00016e
DO - 10.1039/c5md00016e
M3 - Article
SN - 2040-2511
VL - 6
SP - 1081
EP - 1085
JO - MedChemComm
JF - MedChemComm
ER -