Nanoscale Topography Dictates Residue Hydropathy in Proteins.

Abstract

Proteins exhibit diverse structures, including pockets, cavities, channels, and bumps, which are crucial in determining their functions. This diversity in topography also introduces significant chemical heterogeneity, with polar and charged domains often juxtaposed with nonpolar domains in proximity. Consequently, accurately assessing the hydropathy of amino acid residues within the intricate nanoscale topology of proteins is essential. This study presents quantitative hydropathy data for 277,877 amino acid residues, computed using the Protocol for Assigning a Residue's Character on a Hydropathy (PARCH) scale. Leveraging this data set comprising 1000 structurally diverse proteins sourced from the Protein Data Bank, we examined residues situated in various nanoscale environments and analyzed hydropathy in relation to protein topography. Our findings indicate that the hydropathy of a residue is intricately linked to both its individual characteristics and the geometric features of its neighboring residues in response to water. Changes in the number and chemical identity of the neighbors, as well as the nanoscale topography surrounding a residue, are mirrored in its hydropathy profile. Our calculations reveal the intricate interplay of hydrophilic, hydroneutral, and hydrophobic residues distributed across the surface and core of proteins. Notably, we observe that protein surfaces can be ten times more hydrophilic than their cores.