(738e) 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. Low molecular weight PEG at dilute concentrations induces attractive protein-protein interactions. However, the strength of these attractive interactions weakens with increasing PEG concentration and molecular weight. Molecular thermodynamic mechanisms to explain the induced protein-protein interaction and its dependence on PEG molecular weight, as well as the unique solution thermodynamic properties of aqueous PEG solutions - unlimited solubility of PEG in water, lower critical solution temperature behavior, and the concomitant solubility of PEG in organic solvents - have invoked water hydrogen bonding, hydrophobic interactions, and the amphiphilic character of PEG coupled with the influence of polymer conformations. In this work, we calculate the hydration free energy of the PEG dimer, 1,2-dimethoxyethane (DME) using a quasi-chemical (QC) theory approach based on the inverse form of the Potential Distribution Theorem (PDT). This approach enables calculation of the hydration free energy directly from simulation data and without imposing the separation of molecular interactions into reference and perturbation contributions dictated by van der Waals theories of solvation [1, 2]. The calculated hydration free energy of DME is in good agreement with the experimental value. In addition, using this QC theory/PDT approach, we are able to identify the relative contributions of hydrophobic and short-ranged chemical interactions to the calculated free energy of hydration. The influence of DME conformations on this free energy of hydration was also investigated using a multi-Gaussian extension of the PDT [3] to derive contributions to the free energy of DME hydration arising from different polymer conformations in solution. The extension of this analysis to higher molecular weight PEG oligomers and the underlying molecular mechanisms for attractive protein-protein interactions in aqueous solution induced by PEG additives will be also be presented.

References

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