Fig. 1: Rational design of signalling activity through de novo solvent-mediated interaction networks. | Nature Chemistry

Fig. 1: Rational design of signalling activity through de novo solvent-mediated interaction networks.

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

Fig. 1

a, Dynamic remodelling of the solvent-mediated allosteric network during the activation of the μ-opioid receptor (mOR). The positions of water molecules and hydrogen bonds were extracted from the inactive (Protein Data Bank (PDB): 4DKL) and active (PDB: 5C1M) mOR structures. b, Schematic representation of a water-mediated hydrogen bond network bridging four helices designed using the SPaDES software. De novo amino acid sequences, conformations and water positions were searched concurrently for optimal water-mediated hydrogen bond connectivity at the helical interface. c, Snapshot of a low-energy water-mediated hydrogen bond network ensemble in the core of a GPCR structure. d–f, Computational design strategies for enhancing protein activity and conformational stability following three criteria: shifts in conformational energies (d), increased water-mediated dynamic contacts in the active state (e) or weakened ion-mediated locks in the inactive state (f).

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