A new force field including charge directionality for TMAO in aqueous solution.

We propose a new force field for trimethylamine N-oxide (TMAO), which is designed to reproduce the long-lived and highly directional hydrogen bond between the TMAO oxygen (O_TMAO) atom and surrounding water molecules. Based on the data obtained by ab initio molecular dynamics simulations, we introduce three dummy sites around O_TMAO to mimic the O_TMAO lone pairs and we migrate the negative charge on the O_TMAO to the dummy sites. The force field model developed here improves both structural and dynamical properties of aqueous TMAO solutions. Moreover, it reproduces the experimentally observed dependence of viscosity upon increasing TMAO concentration quantitatively. The simple procedure of the force field construction makes it easy to implement in molecular dynamics simulation packages and makes it compatible with the existing biomolecular force fields. This paves the path for further investigation of protein-TMAO interaction in aqueous solutions. [ABSTRACT FROM AUTHOR]