On the smoothing of free energy landscape of solute molecules in solution: A demonstration of the stability of glycine conformers via ab initio QM/MM free energy calculation

Using ab initio QM/MM–MD method, the free energetic (FE) stability of neutral form (NF) glycine conformers was investigated. In the gas phase, the potential energies (PEs) become more destabilized substantially as the dipole moments increase, whereas in aqueous solutions the FEs are stabilized. The stabilization due to its electrostatic interaction with solvent water molecules should adequately compensate for the PE destabilization, and the FEs then become more stabilized in comparison with those by the CPCM method. We conclude for the first time that the FE landscape of NF glycine conformers in aqueous solutions is rather flat.