Free energy surface for rotamers of cis-enol malonaldehyde in aqueous solution studied by molecular dynamics calculations

Abstract

Two-dimensional free energy surfaces for four rotamers of cis-enol malonaldehyde in water have been investigated by umbrella sampling molecular dynamics (MD) calculations. Biasing potential used in the umbrella sampling calculation was adopted to be the minus of conformational free energy preliminary obtained by the thermodynamic integration MD calculations for the rigid malonaldehyde whose stretching and bending were all fixed. The calculated free energy surface shows that, in water, a rotamer that has an intramolecular hydrogen bond is most stable among the rotamers. This is the same as that in vacuum, while order of relative stability of the other three rotamers is different in water and in vacuum. Inclusion of intramolecular vibrations changed the free energy surface little, i.e. at most 2.6 kJ/mol, which is much smaller than the solvation free energy. Free energy barriers from the most stable intramolecular hydrogen bonded rotamer to the others are lowered by hydration but they are still very high, >50 kJ/mol, such that the malonaldehyde molecule spends most of its time in water taking this conformation. Thus, reaction coordinate for intramolecular proton transfer reaction in water may be constructed assuming this rotamer.

Keywords::

• malonaldehyde
• torsional free energy surface
• molecular dynamics calculation
• umbrella sampling method
• thermodynamic integration method

Acknowledgements

This work was supported by TCCI/CMSI in the Strategic Programs for Innovative Research, MEXT, Japan. The calculations were partly performed at the Research Center for Computational Science, Okazaki, Japan, the Center for Computational Sciences, the Supercomputer Center, the Institute for Solid State Physics, the University of Tokyo and the Research Institute for Information Technology, Kyushu University.