The observed improvement was less pronounced for Amber14SB (AUE without coupling: Previous work has assessed the ability of different MD-based approaches to predict cysteine pK a values; we can compare our performance on the overlapping datasets. For 18 cysteine residues, Awoonor-Williams and Rowley, found a thermodynamic integration, replica-exchange scheme with the CHARMM36 force field gave an AUE of 1.67±0.40 pK (compared to 1.64±0.40 pK with CHARMM36m and NES). More recently, Awoonor-Williams and co-workers found that on 25 residues, a Monte Carlo, constant-pH approach paired with CHARMM36m gave an AUE of 2.42 ± 0.36 pK (compared to 1.70 ± 0.34 pK with CHARMM36m and NES).