Table 1.
Comparison of ligand-residue interactions. Percentages of time that the interactions formed are reported using the longest trajectory for each complex
| AA2AR residues | Agonists | Inverse agonists | |||||
|---|---|---|---|---|---|---|---|
| ADN | NEC | UKA | ZMA | XAC | CFF | ||
| Lower region | Trp2466.48 a | 20 | 9 | 8 | - | - | - |
| Thr883.36 b | 58 (82) | 73 (91) | 100 (100) | 0 (1) | 0 (6) | 0 (4) | |
| Asn1815.42 b | 42 (73) | 2 (15) | 10 (41) | 2 (5) | - | - | |
| Ser2777.42 b | 30 (63) | 33 (56) | 100 (100) | - | - | 0 (8) | |
| His2787.43 b | 20 (83) | 64 (94) | 99 (100) | 0 (5) | - | 0 (31) | |
|
| |||||||
| Middle region | Val843.32 c | 76 | 83 | 100 | 72 | 97 | 90 |
| Leu853.33 c | 78 | 89 | 100 | 89 | 77 | 59 | |
| Phe1685.29 d | 94 | 71 | 100 | 100 | 72 | 96 | |
| Glu1695.30 b | 34 (83) | 19 (75) | 1 (39) | 51 (93) | 0 (23) | 4 (37) | |
| Met1775.38 c | 65 | 57 | 97 | 87 | 89 | 45 | |
| Leu2496.51 c | 61 | 80 | 100 | 100 | 75 | 48 | |
| His2506.52 d | 2 | - | - | 97 | - | - | |
| His2506.52 b | 53 (95) | 3 (30) | 54 (86) | 22 (39) | 5 (19) | 6 (13) | |
| Asn2536.55 b | 38 (87) | 26 (79) | 6 (18) | 100 (100) | 80 (95) | 88 (94) | |
| Ile2747.39 c | 21 | 78 | 100 | 98 | 70 | 44 | |
|
| |||||||
| Upper region | Ser61.30 b | - | - | 18 (26) | 5 (8) | 0 (2) | - |
| Tyr91.33 b | 1 (9) | 10 (65) | 85 (94) | 0 (3) | 1 (24) | - | |
| Ile101.34 c | - | - | 43 | - | 1 | - | |
| Glu131.37 b | 2 (8) | 7 (76) | 20 (72) | 0 (2) | 6 (10) | 0 (1) | |
| Ala632.61 c | 18 | 57 | 82 | 3 | 88 | 75 | |
| Ile642.62 c | - | - | 43 | - | 1 | - | |
| Ile662.64 c | 10 | - | 21 | 10 | 98 | 89 | |
| Ser672.65 b | 46 (83) | 33 (88) | 58 (91) | 7 (78) | 47 (80) | 4 (48) | |
| Thr682.66 b | - | - | 6 (8) | - | - | - | |
| Leu2677.32 c | - | - | 81 | 64 | 76 | - | |
| Met2707.35 c | 10 | 24 | 100 | 95 | 79 | 43 | |
| Tyr2717.36 b | - | 2 (19) | 9 (50) | 45 (48) | 4 (24) | 0 (1) | |
Close contact: distance between one heavy atom in the ligand and one heavy atom in the Trp2466.48 side chain within 3.6 Å. A relatively short cutoff was chosen here to reflect the unusually close contacts, approximated to the sum of van der Waals radii for two CH groups.
Polar contact: we define a direct contact if the distance from one N or O atom in the ligand to one N or O atom in the protein side chain within 4.2 Å; the indirect contact is defined if the distance between the two closest polar atoms is greater than 4.2 Å, but there is at least one water molecule that forms hydrogen bonds (heavy atom distance < 4.2 Å) to both atoms. The number in parentheses represents the percentage of time with either direct or indirect contact.
Nonpolar contact: distance from a nonpolar atom in the ligand to another nonpolar atom in the side chain within 5.0 Å. The nonpolar atoms are defined as heavy atoms with partial charges whose absolute values are less than 0.30 electron unit.
π-π stacking contact: distance between the centers of the aromatic core in the ligand and the aromatic side chain within 6.5 Å. The cutoff was chosen to include both the parallel and T-shape π-π interactions.