Estimation of Hydration Free Energy for Polyethylene Glycol Oligomers and the Relative Contributions of Hydrophobic and Short-Ranged Chemical Interactions

Polyethylene glycol (PEG) is a non-ionic water soluble polymer that is used as an additive in protein solutions to induce protein crystallization. PEG in dilute solution concentrations and within a molecular weight range, induces an attractive protein-protein interaction. However the strength of this attractive proteinprotein interaction weakens with increasing PEG concentration and molecular weights. Understanding the solvation thermodynamics of PEG is crucial to understanding the molecular mechanisms for the induced protein-protein interaction and its dependence on PEG molecular weights. We calculate the hydration free energy of 1,2-Dimethoxyethane the shortest oligomer of Polyethylene glycol, using an approach similar to Quasi-chemical theory[1, 2]. This approach enables us to calculate the hydration free energy directly from the simulation data and overcome the limitation in van der Waals approach of identifying a suitable reference interaction model. Using this approach we rearrange the estimation of excess chemical potential into a packing contribution of DME molecule in solvent and an interaction contribution due to explicit interaction of DME with solvent. Thus we are able to estimate the relative contributions of hydrophobic, short-ranged chemical interactions identified by quasi-chemical theory and long-ranged interactions to the overall hydration free energy of DME. The hydration free energy of DME was estimated to be 5.14 kcal/mole, which is in good agreement with experimental result[3]. Influence of ether conformations on solvation of DME was studied by estimating the excess chemical potential for some of the most probable conformers in solution.