Theoretical pKa prediction of O-phosphoserine in aqueous solution

The ability of the polarisable continuum model (PCM) to reproduce aqueous pKas of O-phosphoserine (P-Ser) was checked with Density Functional Theory calculations (B3LYP and M06-2X functionals combined with 6-31+G(d) and 6-31+G(d,p) basis sets). B3LYP/6-31+G(d,p) calculations using the SMD solvation model provide an excellent agreement with experiment. Explicit inclusion of four water molecules solvating the amino acid is mandatory for accurate pKa prediction. Neutral P-Ser conversion to zwitterion in aqueous solution is an extremely rapid process. Activation free energies obtained with a similar methodology as the pKas are very low and reaction free energies suggest that almost complete conversion takes place.