Extending the PARCH Scale: Assessing Hydropathy of Proteins across Multiple Water Models.

Abstract

Quantitative assessment of amino acid hydropathy can be done using the protocol for assigning a residue's character on a hydropathy (PARCH) scale, which assigns values from 0 to 10, with lower values indicating greater hydrophobicity. The merit of the PARCH scale lies in its ability to integrate both the nanoscale topographical features and the chemical properties of amino acid residues when determining hydropathy. In its initial application, we employed the TIP3P water model, optimized for CHARMM36m proteins, to simulate the water behavior around the protein surface. Due to the growing use of the PARCH scale, we have extended its application to three additional all-atom water models: TIP4P, TIP4P-Ew, and TIP5P. Our findings reveal that although PARCH values vary across these water models, the relative hydropathy trends remain consistent. All models successfully distinguished hydrophobic from hydrophilic regions in nanoscale topography, although charged residues showed greater sensitivity to model choice, leading to more significant value variances. Additionally, we evaluated the influence of two other parameters─the force constant used to constrain proteins and the time step of the evaporation process─on the PARCH scale. Overall, the PARCH scale has demonstrated robustness in capturing protein hydropathy across various water models, suggesting its potential applicability with other protein-water force field combinations and even molecular systems beyond proteins.