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.

The smoothing of free energy landscape of neutral form glycine conformers (I-VIII type) in aqueous solution via ab initio QM/MM free energy calculation (ab initio QM/MM-MD simulation vs. dielectric continuum model).130Highlights► Free energy stability of neutral glycine conformers was investigated. ► By ab initio QM/MM-MD method, the free energy landscape was shown to be rather flat. ► The gas-phase potential energies become more destabilized as dipole moments increase. ► However, in aqueous solution, the free energies become more stable inversely. ► The electrostatic stabilization should compensate adequately for the destabilization.