Solvation thermodynamics from cavity shapes of amino acids

According to common physical chemistry wisdom, the solvent cavities hosting a solute are tightly sewn around it, practically coinciding with its van der Waals surface. Solvation entropy is primarily determined by the surface and the volume of the cavity while enthalpy is determined by the solute-solvent interaction. In this work, we challenge this picture, demonstrating by molecular dynamics simulations that the cavities surrounding the 20 amino acids deviate significantly from the molecular surface. Strikingly, the shape of the cavity alone can be used to predict the solvation free energy, entropy, enthalpy, and hydrophobicity. Solute-solvent interactions involving the different chemical moieties of the amino acid, determine indirectly the cavity shape, and the properties of the branches but do not have to be taken explicitly into account in the prediction model.

Automated summary

According to traditional physical chemistry wisdom, solvent cavities tightly wrap around solutes, practically coinciding with their van der Waals surface. However, this study challenges this notion by demonstrating that the cavities surrounding 20 amino acids deviate significantly from the molecular surface. Remarkably, the shape of the cavity alone can predict solvation free energy, entropy, enthalpy, and hydrophobicity, without explicitly considering solute-solvent interactions involving the different chemical moieties of the amino acid in the prediction model.