van der Waals Dispersion Forces and Hydrophobic Solvation

Per definition hydrophobic compounds are averse to aqueous environments. Peculiar examples are non-polar moieties or conformations of biomolecules, which are inevitably exposed to water under physiological conditions. Therefore, an accurate description of the interactions in such an unfavorable setup, in terms of solvation, is of paramount importance to comprehend the biomolecular machinery. One major source of attractive interaction between non-polar entities and water is van der Waals (vdW) dispersion forces. These weak interactions form the basis of biochemical functionality as they give rise to the necessary conformational flexibility. Typically, vdW forces, emerging from instantaneous fluctuations of the electron density, are only phenomenologically included in solvation models. In this contribution, we address the relevance of their intrinsic many-body character for hydrophobic solvation. In our study, we employ a combined approach of the Density-Functional Tight-Binding method and the Many-Body Dispersion model. The findings show that collective charge fluctuations contribute significantly to a distinct conformational dependence of the stability of (bio)molecular solutes in water. Ultimately, this leads to a considerable decrease of energy barriers during protein folding.