Table 1.
A comparison of the conformational changes observed in microsecond MD simulations including lemborexant and compound 1.
| Conformational change | Compound 1 replica 1/2/3* | Lemborexant replica 1/2/3 |
|---|---|---|
| Ligand position in the receptor binding site | No change | No change/no change/slight change |
| ECL2 closing | Yes/yes/yes | Yes/yes/yes |
| Changes of macroswitch III | Yes/no/no | Yes/yes/no |
| Changes of AHD position (opening of Gα) | Yes/no/yes | Yes/yes/yes |
| Formation of the GDP/GTP exchange tunnel | Yes/no/no | Yes/yes/no |
| Active-like direction of rotation of N-terminal helix of Gα like in NTSR1 | Yes/no/no | No/no/no |
| Changes of macroswitch I to ‘on’ with R183G.hfs2.02 movement away from GDP | Yes/yes/yes | Yes/yes/yes |
| Changes of F341G.H5.08 microswitch to ‘on’ | Yes/no/no | Yes/yes/no |
| Changes of D277G.HG.02 microswitch to ‘on’ | Yes/yes/yes | Yes/yes/yes |
*If differences between replicas were observed.