Table 1.
Comparison of acylation energy barriers of the current and previous works.
| Sourcea | Energy barriers (kcal mol−1)b | Methodc | ||
|---|---|---|---|---|
| MC-TI | TI-AE | Overall | ||
| This study | 3.6(3) | 11.4(1) | 11.4(1) | DFTB3/mio:CHARMM, CoS |
| This study | 4.4(5) | 3.3(1) | 7.1(5) | B3LYP/6–31G:CHARMM, CoS |
| This study | 7.9(7) | 3.8(2) | 10.9(4) | B3LYP/6–31+G*:CHARMM, CoS |
| This study | 8.6(9) | 3.8(7) | 11.9(4) | B3LYP/6–31++G**:CHARMM, CoS |
| This study | 5.7(8) | 3.4(3) | 8.0(3) | B3LYP-D3/6–31++G**:CHARMM, CoS |
| This study | 9.1(3) | 3.9(7) | 12.7(3) | B3LYP/6–311++G**:CHARMM, CoS |
| This study | 6.2(4) | 3.6(8) | 9.0(1) | B3LYP-D3/6–311++G**:CHARMM, CoS |
| Pitarch et al.16,d | 18.2(9) | 12.9(1) | 18.2(9) | AM1:CHARMM, IRC |
| Hermann et al.17 | 19.6 | 16.4 | 19.6 | AM1:CHARMM, PESs |
| Hermann et al.17 | 8.7 | 7.1 | 8.7 | B3LYP/6–31+G*:CHARMM, PESs |
| Meroueh et al.18,d | 22.0 | N/De | 22.0 | MP2/6–31+G*:AMBER, PESs |
| Gibson et al.12 | N/A | N/A | 12.6(7) | 293.15 K, Exp |
| Sirot et al.13 | N/A | N/A | 13.0(5) | 310.15 K, Exp |
| Cheong et al.14 | N/A | N/A | 12.7(0) | 293.15 K, Exp |
aComputational acylation reaction profiles are constructed for the mechanism with Glu166 as a general base. The computational result with the best experimental compliance is marked in bold.
bMC-TI: Michaelis complex to tetrahedral intermediate; TI-AE: tetrahedral intermediate collapsing to acyl-enzyme product;
cCoS chain-of-states calculation, the reported barrier is the average value over 18 pathways; IRC intrinsic reaction coordinate calculation, PESs potential energy surface scan, Exp derived from experimental kcat under the specified temperature;
dThis study uses penicillanic acid instead of benzylpenicillin, the experimental acylation barrier of penicillanic acid is estimated to be 16–17 kcal mol−1;
eBarrier was reported to be “inconsequentially small”.