Figure 4.

Network analysis identified impacts on several key structural motifs by the presence of LY3154207 in the D1R/dopamine systems. (A) A network connecting residues with larger than 0.2 contact frequency in the D1R/dopamine-LY3154207 condition. If the shortest heavy-atom distance between two residues was within 4.5 Å, we defined that they formed a contact. Edge radii are scaled by contact frequency. (B) Top and (C) side views of the D1R/dopamine-LY3154207 system with the residue nodes colored and scaled in radius according to the eigenvector centrality scores. All nodes with an absolute score difference exceeding 0.005 between the D1R/dopamine-LY3154207 and D1R/dopamine-alone conditions are highlighted in color. Thus, this eigenvector centrality analysis demonstrates that the presence of LY3154207 resulted in higher scores (yellow) for residues in the extracellular region enclosed by TMs 1, 2, 3, and 7, and lower scores (green) for residues in the intracellular region. Note that in addition to the TM residues discussed in text, S188^EL2 has a significantly higher score in the LY3154207-bound D1R/dopamine-alone condition. Upon further inspection, we observed that this residue moved downward into the OLBP and interacted with the charged nitrogen of dopamine. However, this interaction was not observed in D1R/apomorphine-LY3154207 condition since the bulky rings of apomorphine preclude such a movement of S188^EL2.