Interaction-component analysis of the urea effect on amino acid analogs

Abstract

Transfer energetics from pure water to a urea–water mixture is examined for a set of amino acid analog solutes by using molecular dynamics simulation and free-energy calculation. The free energy of transfer from pure-water solvent to 8 M urea–water mixed solvent is calculated for each solute, and the urea–water mixture is shown to be a more favorable solvent than pure water. The correlation of the transfer free energy is then examined against the corresponding changes upon transfer of the average sum of solute–solvent interaction energy and its electrostatic and van der Waals components. A strong correlation is observed against the change in solute–solvent energy, with a dominant contribution from the van der Waals component for neutral solutes. The electrostatic component exhibits a weak correlation due to the compensation between the contributions from urea and water. The transfer free energy is further decomposed into the contributions from urea and water within an approximate framework of the energy-representation theory of solvation. It is found that urea makes a favorable contribution to the transfer free energy. The contribution from water depends on the hydrophobicity/hydrophilicity of the solute. Urea and water act cooperatively for hydrophobic solute, and are competitive against each other for hydrophilic solute. The effect of excluded volume is also addressed, and is seen to be minor in the transfer energetics due to the compensation between the contributions from urea and water.