Molecular representations were made using PyMOL (DeLano Scientific) with PDB files 2GIX (IRK1-MPD), 2E4F(GIRK2) and 2QKS (Kirbac1.3-GIRK1). The cavity of the IRK1-MPD pocket was calculated using CASTp server49 with 1.4 Å probe radius. L245W was modeled in the IRK1-MPD structure by optimizing the best rotamer position for Trp using PyMOL software. Molecular volume estimates for amino acid side-chains were based on reported values50.
