Abstract
Hydration thermodynamics play a fundamental role in fields ranging from the pharmaceutical industry to environmental research. Numerous methods exist to predict solvation thermodynamics of compounds ranging from small molecules to large biomolecules. Arguably the most precise methods are those based on molecular dynamics (MD) simulations in explicit solvent. One theory that has seen increased use is inhomogeneous solvation theory (IST). However, while many applications require accurate description of salt–water mixtures, no implementation of IST is currently able to estimate solvation properties involving more than one solvent species. Here, we present an extension to grid inhomogeneous solvation theory (GIST) that can take salt contributions into account. At the example of carbazole in 1 M NaCl solution, we compute the solvation energy as well as first and second order entropies. While the effect of the first order ion entropy is small, both the water–water and water–ion entropies contribute strongly. We show that the water–ion entropies are efficiently approximated using the Kirkwood superposition approximation. However, this approach cannot be applied to the water–water entropy. Furthermore, we test the quantitative validity of our method by computing salting-out coefficients and comparing them to experimental data. We find a good correlation to experimental salting-out constants, while the absolute values are overpredicted due to the approximate second order entropy. Since ions are frequently used in MD, either to neutralize the system or as a part of the investigated process, our method greatly extends the applicability of GIST. The use-cases range from biopharmaceuticals, where many assays require high salt concentrations, to environmental research, where solubility in sea water is important to model the fate of organic substances.
Highlights
“Water, water, every where, ne any drop to drink”, the ancient mariner cries out in Samuel Coleridge’s poem [1,2,3,4,5]
We find that the N a+ entropy around carbazole is consistently positive, indicating a reduced density compared to bulk
The thermodynamics of solvation are crucial in many fields, such as the pharmaceutical industry or environmental research
Summary
“Water, water, every where, ne any drop to drink”, the ancient mariner cries out in Samuel Coleridge’s poem [1,2,3,4,5]. Ions influence the melting temperature [14] and conformations [15] of DNA, as well as the stability of proteins in solution, an effect that is described by the Hofmeister series [16] It has been shown that results from Affinity-Capture Self-Interaction Nanoparticle Spectroscopy (AC-SINS) [19] correlate with HIC experiments only when sufficient salt concentrations are used. This is expected since long-range electrostatic interactions are shielded, while hydration of hydrophobic side chains as well as the protein backbone is disfavored by the salting-out effect [20]. For in-depth analysis of solvation effects, it is desirable that those methods provide separate contributions of energy and entropy to the free energy of solvation, as well as a spatial resolution of the computed properties [21]
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