A2aR Oligomeric assemblies identified from MD simulations using in-vivo mimetic biomembranes

GPCR oligomerisation is known to play an important role in the receptor signalling. However, due to the technical challenges, the structural information of GPCR oligomerisation is still very limited, which hinders our understanding of GPCR signalling in a fuller picture. In this deposit, we provide the structural coordinates of various oligomeric assemblies (up to pentamers) of Adenosine A2a receptor that were sampled from unbiased MD simulations.

For more information regarding the MD simulation setup and definitions of the various calculated values, please check out our paper on BioRxiv: https://www.biorxiv.org/content/10.1101/2020.06.24.168260v1

** Simulation setup **
9 copies of A2aR were randomly inserted into an in-vivo mimetic biomembrane to build the initial configuration of the simulations. 10 such systems were set up for A2aR in the inactive state and 10 for the active state. The systems were represented by MARTINI 2 coarse-grained models and were simulated for 50 micro-seconds. The use of MARTINI coarse-grained force field would freeze the receptor conformation as in the initial configuration, thus decoupled the oligomerization from such processes as ligand-induced conformational change. The more efficient sampling of coarse-grained force field therefore allowed us to explore efficiently the protein-protein associations in the oligomerisation process. Protein-protein  associations were identified when any atoms from two protomers were getting closer than 0.75 nm. The oligomerisation process was monitored and the sampled oligomeric assemblies were stored.

** Coordinate file explained **
The coarse-grained oligomeric structures were converted back to atomistic model in CHARMM force field. Oligomeric assemblies of the same oligomeric state (OS) were clustered to identify the different arrangements. 100 oligomeric arrangements (or all of the sampled oligomers if the cluster contains less than 100 samples) were randomly taken from each cluster and stored as seperate models in a pdb coordinate file. The pdb coordinate files were named as {Conf. State}_OS{Oligomeric State}_cl{Cluster id}.pdb, and can be viewed by such visualization tools as PyMol, Chimera or JMol etc. A Excel file containing some statistics of the oligomeric assemblies were also provided.