Fig. 6: Hyd-high7 is built of a synthetic allosteric interaction network distant from those of natural GPCRs. | Nature Chemistry

Fig. 6: Hyd-high7 is built of a synthetic allosteric interaction network distant from those of natural GPCRs.

From: Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks

Fig. 6

a,b, Solvent-mediated polar interaction networks at static–switchable TMH interfaces in mOR (PDB: 5C1M) (a) and Hyd_high7 (b) active-state X-ray structures. Water molecules are represented as red spheres and water-mediated hydrogen bonds are indicated by yellow dotted lines. c,d, Interhelical (direct and water-mediated) polar interactions in the TMH core region extracted from the mOR (5c1m) (c) and Hyd_high7 (d) active-state X-ray structures viewed perpendicular to the membrane bilayer. Polar interactions are represented as dotted red lines on the backbone representation of the receptors. The designed mutations rewired the inter-TMH polar interaction network by eliminating native polar contacts between TMH3 and TMHs 5–7 while enhancing TMH7 connections with neighbouring TMHs 1, 2 and 6.

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