Comparing Alchemical Free Energy Estimates to Experimental Values Based on the Ben-Naim Formula: How Much Agreement Can We Expect?

by Rogers, T. Ryan; Wang, Feng

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The solvation free energy (SFE) plays a key role in thermodynamics. One well-established method for computing the SFE is through an alchemical transformation. However, experimental SFEs are generally determined according to the Ben-Naim equations relying on vapor pressure or density ratios. It is important to establish whether, or to what extent, typical alchemical-based free energy computations provide results comparable to experimental SFEs. In this work, we mimic experimental measurements by simulating the liquid -vapor coexistence of water without alchemical operations. The SFEs measured through vapor pressure and density ratios are used to validate the SFEs obtained through alchemical transformations. It is shown that proper consideration of the nonideal behavior of the vapor is important to ensure that the alchemical SFEs are consistent with the Ben-Naim SFEs. Alchemical transformations in the vapor phase should be performed in addition to solution phase transformations for strongly interacting solutes, such as those with low boiling temperatures and large second virial coefficients. A formula based on the virial expansion of pressure is proposed to provide a better estimate of the true SFE from the simulated vapor pressures. The proposed formula is also applicable to experimental determinations of SFE when the pressure-based route is used.

Journal
Journal of Physical Chemistry B
Volume
124
Issue
5
Year
2020
Start Page
840
ISBN/ISSN
1520-6106; 1520-5207
PMID
31922746
DOI
10.1021/acs.jpcb.9b08965