Table 2. Properties from the MD simulations WT, A22S, A52T, and V108M COMT.
| Property a | WT COMT | A52T COMT | A22S COMT | V108M COMT |
|---|---|---|---|---|
| Cα-rmsd (Å) | 3.1 ± 0.2 | 2.9 ± 0.3 | 4.0 ± 0.5 h | 3.7 ± 0.4 h |
| Total SASA (Å2) b | 11344 ± 245 | 11290 ± 329 | 11759 ± 277h | 11850 ± 263 h |
| SAM-Binding Site SASA (Å2) c | 989 ± 105 | 968 ± 180 | 965 ± 180 | 1150 ± 79 h |
| Catechol-Binding Site SASA (Å2) d | 937 ± 77 | 924 ± 30 | 1088 ± 30 i | 851 ± 96 |
| W38 Cγ - P174 Cγ (Å) | 19.0 ± 1.8 | 21.2 ± 2.3 | 22.8 ± 1.6 h | 23.7 ± 4.8 |
| A52T Polymorphic Site | ||||
| Polymorphic Site SASA (Å2) e | 427 ± 49 | 434 ± 41 | 393 ± 15 | 392 ± 20 |
| A/T 52 Cβ – I49 Cγ2 (Å) | 5.8 ± 0.5 | 6.2 ± 0.4 | 6.0 ± 0.4 | 6.0 ± 0.4 |
| A/T 52 Cβ – I54 Cβ (Å) | 7.4 ± 0.2 | 7.4 ± 0.2 | 7.5 ± 0.2 | 7.4 ± 0.2 |
| A/T 52 Cβ – Q55 Cβ (Å) | 5.6 ± 0.4 | 5.7 ± 0.4 | 5.6 ± 0.4 | 6.0 ± 0.5 |
| A52 Cβ /T52 Cγ2 – E56 Cγ (Å) | 6.0 ± 0.7 | 5.2 ± 0.9 | 6.5 ± 0.8 | 5.8 ± 0.9 |
| A/T 52 Cβ – Y194 Cε2 (Å) | 7.5 ± 0.9 | 7.8 ± 1.1 | 6.7 ± 1.1 | 8.1 ± 1.0 |
| A22S Polymorphic Site | ||||
| Polymorphic Site SASA (Å2) f | 318 ± 86 | 299 ± 33 | 386 ± 37 | 392 ± 63 |
| Helix α2 Cα-rmsd (Å) | 0.5 ± 0.1 | 0.4 ± 0.1 | 0.5 ± 0.1 | 0.4 ± 0.1 |
| Helix α4 Cα-rmsd (Å) | 0.9 ± 0.3 | 0.7 ± 0.1 | 1.0 ± 0.3 | 0.6 ± 0.2 |
| A/S 22 Cβ – V74 γ1 (Å) | 4.9 ± 0.7 | 4.5 ± 0.5 | 7.0 ± 3.1 | 7.2 ± 1.3 h |
| A/S 22 Cβ – R78 Cγ (Å) | 4.5 ± 0.6 | 5.4 ± 1.3 | 10.5 ± 3.8 h | 8.2 ± 2.5 h |
| A/S 22 Cβ – A106 Cβ (Å) | 6.4 ± 2.4 | 4.9 ± 0.6 | 5.3 ± 0.9 | 4.9 ± 0.8 |
| A22 Cβ / S22 Oγ – G107 Cα (Å) | 8.9 ± 3.0 | 7.2 ± 0.8 | 5.7 ± 1.0 | 6.5 ± 0.7 |
| A/S 22 Cβ – V108 Cγ1/ M108 Sδ (Å) | 6.3 ± 3.0 | 4.6 ± 0.7 | 5.3 ± 1.4 | 4.8 ± 0.8 |
| V108M Polymorphic Site | ||||
| Polymorphic Site SASA (Å2) g | 384 ± 95 | 369 ± 31 | 425 ± 41 | 452 ± 38 |
| V108 Cγ1/ M108 Sδ – A22 Cβ (Å) | 6.3 ± 3.0 | 4.6 ± 0.7 | 5.3 ± 1.4 | 4.9 ± 0.7 |
| V108 Cγ1 – L26 Cδ1/ M108 Cε - L26 Cδ2 (Å) | 11.7 ± 1.7 | 10.2 ± 0.8 | 7.2 ± 2.0 i | 7.0 ± 1.5 i |
| V108 Cγ2 /M108 Sδ – A73 Cβ (Å) | 5.0 ± 1.1 | 4.6 ± 0.5 | 6.5 ± 2.0 | 6.6 ± 2.2 |
| V108 Cγ2 /M108 Cε – V74 Cγ1 (Å) | 7.6 ± 2.5 | 5.2 ± 0.8 | 5.2 ± 0.9 | 6.0 ± 1.3 |
| V108 Cγ1 /M108 Sδ – A77 Cβ (Å) | 5.2 ± 1.3 | 4.2 ± 0.6 | 6.6 ± 3.1 | 5.0 ± 1.4 |
| V108 Cγ1 /M108 Sδ – R78 Cβ (Å) | 8.4 ± 3.1 | 7.6 ± 1.4 | 9.3 ± 1.3 | 8.5 ± 2.0 |
| V108 Cγ2 /M108 Cε – V103 Cγ1 (Å) | 4.9 ± 0.9 | 4.3 ± 0.3 | 4.3 ± 0.3 | 6.4 ± 2.0 |
| V108 Cγ2 /M108 Cε – A106 Cβ (Å) | 4.5 ± 0.4 | 4.2 ± 0.4 | 4.2 ± 0.3 | 4.8 ± 0.8 |
All values were calculated using structures from the last 5 ns of each simulation. All values are expressed as means and standard deviations of the means from three independent simulations at 37°C.
The total solvent-accessible surface area (SASA) was determined using the NACCESS algorithm (65).
The following residues were used to calculate the SASA of the SAM-binding site: A39, M40, N41, V42, G66, A67, Y68, S72, E90, I91, N92, G117, A118, S119, Q120, D141, H142, and W143.
The following residues were used to calculate the catechol-binding site SASA: W38, M40, K46, D141, K144, D169, N170, C173, P174, L198, E199, Y200, and D205.
The following residues were used to calculate the A52T polymorphic site SASA: I49, V53, Q55, E56, Y194, and residue 52.
The following residues were used to calculate the A22S polymorphic site SASA: Q23, V25, L26, V74, A77, R78, A106, residue 108 and residue 22.
The following residues were used to calculate the V108M polymorphic site SASA: residue 22, A73, V74, R78, V103, A106, G107, K109, K111, V112 and residue 108.
p < 0.10.
p < 0.05.