A molecular dynamics study of the effects of salt on the conformational preferences of leucine enkephalin (LE) in water has been performed to outline a general approach for quantifying the effects of a cosolvent on a biomolecular equilibrium in solution using molecular simulation. The simulations of LE suggest that the peptide exists as a mixture of folded and unfolded conformations in pure water, and a potential of mean force calculation indicates the population of the folded form to be 53 +/- 3%. The addition of 2 M salt reduces the population of the folded form to 12 +/- 5%. A combination of the simulation data and Kirkwood-Buff theory is used to determine the preferential interactions of the cosolvent with the peptide and to reproduce the population changes indicated by the potential of mean force calculations. The results demonstrate the potential of a combined simulation and Kirkwood-Buff approach for quantifying simulation data in an effort to understand the effects of cosolvents on the thermodynamics of biomolecules in solution, especially for systems where potential of mean force calculations are unfeasible.