Table 1. Calculated Free Energy Barriers for Meropenem Deacylation in the Class a β-lactamases SFC-1, BlaC, and TEM-1, Including Mutants and Restraints on the 6α-1R-Hydroxyethyl Group. All Free Energy Barriers Were Calculated at the SCC-DFTB/ff12SB Level Using Umbrella Sampling and the Weighted Histogram Analysis Method47.
| enzyme | calculated free energy barrier (kcal/mol)a |
|---|---|
| SFC-1WT(no restraints) | 10.9b |
| SFC-1WT position III | 10.5 |
| SFC-1WT position II | 7.7 |
| SFC-1Cys238Gly position II | 13.8 |
| SFC-1Asn132Gly(no restraints) | 12.5 |
| SFC-1Asn132Gly position II | 14.1 |
| SFC-1Asn132Gly position III | 15.2 |
| SFC-1 Asn132Gly/Cys238Gly (no restraints) | 16.2 |
| BlaC WT(no restraints) | 17.9b |
| BlaC position II | 17.5 |
| BlaC Gly132Asn(no restraints) | 18.2 |
| BlaC Gly132Asn position II(no restraints) | 15.7 |
| BlaC Gly132Asn position II | 14.9 |
| TEM-1WT(no restraints) | 17.1b |
| TEM-1WT position I | 17.3 |
| TEM-1WT position II | 19.1 |
| TEM-1Asn132Gly(no restraints) | 16.4 |
| TEM-1Asn132Gly position I | 17.8 |
| TEM-1Asn132Gly position II | 25.2 |
a
Dihedral restrained to initial position (unless stated otherwise) with a harmonic force constant of 100 kcal mol–1 Å–2.
b
Data taken from Chudyk et al. 2014.40