Urea parametrization for molecular dynamics simulations

Abstract

Although the idea of urea as water structure breaker is widely spread, urea dimer formation is also thought to be an important factor influencing the behavior of urea–water solutions. We use this last idea to obtain a potential for urea to use in molecular dynamic simulations of protein unfolding processes and we compare this with the potentials obtained from density functional theory (DFT). Three potentials for urea are generated. One based on a parametrization for proteins to reproduce substantial dimer formation; and the other two from DFT quantum calculations. Simulations of 2 M and 8 M urea aqueous solutions with the three set of charges were performed. Cyclic dimers with very favorable interactions appear in the simulation with the non-DFT urea potential. Head-to-tail dimer formation occurs too, as found in crystals. This set of charges maintains a good balance between the urea-urea and urea-water interactions, with urea flexibility being important. In the simulations using the quantum derived charge sets dimers are rarely found and with very low interaction energies. Thus, the parametrization obtained from the DFT ab initio calculations is inadequate for molecular dynamics simulations of urea-aqueous solutions. However, the DFT calculations indicate that the urea molecule in water solution may have a planar structure as in the crystal.