Defined-Sector Explicit Solvent in Continuum Cluster Model for Computational Prediction of pKa: Consideration of...

Benchmark accuracy for prediction of first and second dissociation constants (pKa1 and pKa2 values) is realized with the recently developed Defined-Sector Explicit Solvent in Continuum Cluster Model. The model provides a systematic basis for inclusion of explicit solvation, essential for accurate prediction of dissociation constants using computational continuum model approaches. The DSES-CC model is demonstrated by considering the structure-to-chemical affinity relationship of the carboxyl functional group and is shown to provide predictability with mean absolute error of 0.5 pK units across a wide array of carboxylic acid functionality.