Theoretical Study of the Tautomeric/Conformational Equilibrium of Aspartic Acid Zwitterions in Aqueous Solution

Abstract

The present study is the first attempt at the theoretical calculation of the tautomeric/conformational equilibrium for a zwitterionic α-amino acid in aqueous solution. The gas-phase zwitterionic structure for aspartic acid (Asp) does not correspond to a local minimum on the potential energy surface. The optimized geometry was determined for the dihydrated zwitterion at the HF/6-31G* level. Single-point calculations for the isolated zwitterion, with the geometry optimized for the dihydrate, were performed up to the QCISD(T)/6-31G* and MP2/6-311++G** levels. Vibrational-frequency-dependent thermal corrections were calculated for the dihydrates. Relative hydration free energies of the isomeric species were calculated using the free energy perturbation method implemented in Monte Carlo simulations. In a second approach, relative free energies were calculated using the self-consistent isodensity polarizable continuum model (SCIPCM). In aqueous solution, aspartic acid forms two tautomeric zwitterions (α and β),...