Ab Initio Liquid Water Dynamics in Aqueous TMAO Solution.

Area of Science:

• Computational Chemistry
• Physical Chemistry
• Molecular Dynamics

Background:

• Trimethylamine N-oxide (TMAO) is a common osmolyte used to stabilize proteins.
• Understanding the molecular interactions of TMAO with water is crucial for its biological function.
• Previous studies have explored TMAO's effects, but detailed dynamics remain an area of investigation.

Purpose of the Study:

• To elucidate the effects of TMAO on the reorientational dynamics of heavy water (D2O) molecules.
• To investigate the role of hydrogen bonding between TMAO and D2O.
• To compare the accuracy of ab initio molecular dynamics (AIMD) with traditional force field models.

Main Methods:

• Ab initio molecular dynamics (AIMD) simulations of TMAO-D2O solutions.
• Decomposition of D2O molecules into specific subensembles for detailed analysis.
• Calculation of angle-resolved radial distribution functions to assess hydrogen bond directionality.

Main Results:

• AIMD simulations show that TMAO significantly retards D2O reorientational dynamics near its hydrophilic oxygen atom due to O-D···O(TMAO) hydrogen bonds.
• Two distinct mechanisms govern D2O rotation: breaking the hydrogen bond or rotating with TMAO.
• Force field simulations exhibit faster dynamics and fail to capture the strong directionality of the O-D···O(TMAO) hydrogen bond observed in AIMD.

Conclusions:

• AIMD simulations provide a more accurate description of TMAO-water interactions and dynamics compared to force field models.
• The strong directionality of the hydrogen bond, influenced by TMAO's sp3 orbital configuration, is critical for accurate modeling.
• Modeling negatively charged oxygen atoms as single point charges in force fields may inadequately represent hydration and dynamics.