Molecular dynamics simulation of aqueous urea solution: is urea a structure breaker?

An aqueous solution of urea is a very important mixture of biological relevance because of the definitive role of urea as protein denaturant at high concentrations. There has been an extended debate over the years on urea's influence on the structure of water. On the basis of a variety of analysis methods employed, urea has been described as a structure-breaker, a structure-maker, or as neutral toward water structure. Using molecular dynamics simulation and a nearest neighbor approach of analyzing water structure, we present here a detailed analysis of the effect of urea on water structure. By carefully choosing the nearest neighbors, allowing urea also to be a neighbor of a reference water molecule, we have conclusively shown that urea does not break the local tetrahedral structure of water even at high concentrations. A slight change in the distribution of tetrahedral order parameters as a function of urea concentration has been shown to be a result of change in the proportions of n-hydrogen-bonded water molecules. The present result thus suggests that urea is able to substitute for water in the hydrogen-bonded network nicely without breaking the tetrahedral, hydrogen-bonded structure of water.