Seminar room RB35 (Roslagstullsbacken 35, the SBC house)
Description
Recently published structure of Adenosine Receptor A2a complexed with antagonist ZM2413853 (PDB: 3EML) is first protein of the subfamily A16, class A GPCR which structure have been solved with atomic resolution. Thanks to Critical Assessment of GPCR Modeling and Docking Project prediction of this structure could be done on fully blind manner and undergo independent assessment. This case study have been also motivation to construct automatic homology modeling and docking pipeline designed for predictions of TM7 family complexes. Adenosine receptor share no significant homology to Rhodopsin or Adrenergic receptors which where the only GPCR structures available at that time. Structural comparison reveals major differences in binding site composition and ligand binding characteristics making structure prediction and docking of Adenosine receptor challenging task. Presented results show good overall agreement between best ranked model and crystal structure with less than 2.0Å RMSD for TM helices correct pose of the ligand in the binding pocket. The major cavity was lack of disulfide bonds in extracellular loop and overestimated coulombic contribution in total free enery of binding. Even tough, the prediction is not faultless it shows positive perspective for this prediction routine.
