Hydration structure of osmolyte TMAO: concentration/pressure-induced responseElectronic supplementary information (ESI) available. See DOI: 10.1039/c6nj03296f

Despite the well-known fact that the natural osmolyte trimethylamine- N -oxide (TMAO) is able to prevent protein denaturation and to stabilize the folded state of proteins in living cells under abiotic stress, much of its molecular mechanism of action remains elusive. At the moment, there is some evidence that osmolytes, including TMAO, do not interact with proteins directly but only through a water layer. It is supposed that their protective mechanism should be mediated and determined largely by their hydration, i.e. by osmolyte interactions with surrounding water. However, to date the details of these interactions are far from being fully understood. To gain further insight into the mechanism behind the protecting effect of osmolytes statistical mechanics calculations in the framework of 1D- and 3D-RISM (reference interaction site model) approaches were performed to yield information on the impact of solute concentration and pressure on the hydration structure of TMAO. An attempt was made to link the structural features of TMAO hydration to its biological role. The effect of solute concentration/pressure on the TMAO hydration structure was studied to understand its protective action under abiotic stressors.