Conformational free energy surfaces of non-ionized glycine in aqueous solution

Abstract

Ab initio calculations on glycine and quantum mechanical/molecular mechanical molecular dynamics simulations (QM/MM-MD) on solvated non-ionized glycine were performed to explore the free energy landscapes of non-ionic glycine conformers in aqueous solution. Among nine different conformers of glycine, QM/MM-MD simulations found ttc and gtc conformers stable in addition to ttt, ccc, gtt, tct and gct which were well known as stable isomers in pure QM calculation. The stabilities of ttc and gtc come from a strong solvation at their carboxylic group side (–COOH) in solution. The preferred rotation along C–C (φ) as compared to C–O (θ) in both pure QM calculations and QM/MM-MD indicates the importance of intramolecular effects in determining relative free energies. On the other hand, the existence of stable ttc and gtc conformers only in solution phase clearly shows the importance of intermolecular interaction by explicit solvents. The same intermolecular interactions have a mixed effect on the free energy barriers. They reduced the barriers of A (ccc) → B (gtc) and A (ccc) → C (gct) isomerizations as compared to the ab initio or PCM results. At the same time, they also increased the barriers of B (ttc, gtc) → D (ttt, gtt). In short, the conformational free energy surfaces of non-ionized glycine in solution are largely different from the corresponding potential energy surfaces of gas phase. The fact that the initial conformer for tautomerization ccc is stable makes the N → Z tautomerization facile. However, concurrently, diverse conformational isomerizations to ccc make the tautomerization dependent on the isomerizations.