Fig. 2.
The 3DMTR permutation analysis identifies significantly intolerant residues within the RGS domain that were not identified by 1DMTR. (A–C) Raster plot of selected RGS proteins comparing 1DMTR, 3DMTR based on the 31 neighboring residues, 3DMTR based on the 21 neighboring residues, and significantly intolerant residues based on the permutation analysis (rows labeled “c21-sig.”, labeled by a blue rectangle). (D–F) Structural views of RGS domains colored to show a heatmap of the 21-residue 3DMTR score (intolerant residues in blue, neutral in white, tolerant in red) bound to G alpha. (G–I) Structural view of the 21-residue 3DMTR permutation analysis raster plot significantly tolerant/intolerant residues. (J) RGS protein alignment shows the RGS domain (lilac), residues in the hydrophobic core (yellow), residues in direct contact with G alpha (gray), and selected residues to test the functional consequences inside box. The residues with a 3DMTR score >0.5 are determined to be not highly intolerant (tolerant) and the color letter is red. Residues with a 3DMTR score ≤0.5 are determined to be highly intolerant and the color letter is blue. Residues identified via the permutation analysis are identified with symbols * (MTR 0.5, highly intolerant) or ∧ (MTR > 0.5, not highly tolerant).