The protein-stabilizing effects of TMAO in aqueous and non-aqueous conditions.

We present a new water-dependent molecular mechanism for the widely-used protein stabilizing osmolyte, trimethylamine -oxide (TMAO), whose mode of action has remained controversial. Classical interpretations, such as osmolyte exclusion from the vicinity of protein, cannot adequately explain the behavior of this osmolyte and were challenged by recent data showing the direct interactions of TMAO with proteins, mainly hydrophobic binding. Solvent effect theories also fail to propose a straightforward mechanism.