Importance of excluded volume on the solvation of urea in water

We have used molecular dynamics simulations to probe the concentration-dependent solvation of urea in water. Two models of urea are considered: one is the OPLS potential, and the other is the recently introduced KBFF model whose parameters were obtained to reproduce the experimental values of the Kirkwood-Buff integrals. Although the partial charges on the urea atoms in the models are dramatically different, the concentration-dependent structural characteristics of water are similar. The largest difference between the two models is in the prediction of the tendency of urea to self-associate. The OPLS model leads to stronger urea-urea association than the KBFF model. Surprisingly, this difference is traced to the variations in the Lennard-Jones parameters rather than the charge distributions. These results suggest that solvation of urea depends not only on its ability to form hydrogen bonds with water but also its excluded volume. More generally, we propose that the denaturation efficiency of polar nonelectrolytes, such as urea, is determined by the ability of the cosolute to form hydrogen bonds with the polypeptide chain which, in turn, depends on its size.