Fig. 2: Computational-designed GPCRs with a wide range of water-mediated interaction networks at switchable TMH interfaces.
a, Backbone representation of a GPCR scaffold highlighting static (dark grey) and switchable (light grey) TM helices. b, Relationship between the total number of buried water molecules mediating polar contacts and those at static–switchable TMH interfaces. Data for the native A2AR (light grey) are included for comparison. Designs with a higher and lower number of water-mediated static–switchable hydrogen bonds than A2AR are classified as Hyd_high and Hyd_low, respectively. c,d, Hydrogen bond network in the TMH core regions of the Hyd_low2 (c) and Hyd_high4 (d) structures. The positions of the residues highlighted as stick models are indicated by Ballesteros–Weinstein notation. e, Adenosine-induced activity of the designed receptor variants (as a percentage of adenosine-induced WT A2AR activity) as a function of the number of solvent-mediated interactions at static–switchable TMH interfaces. A baseline for the native A2AR (light grey) is included for comparison. The data are presented as the mean ± standard error of the mean (s.e.m.) for n = 3 independent experiments.
