Context Dependency of Hydrophobicity in Intrinsically Disordered Proteins: Insights from a New Dewetting Free Energy-Based Hydrophobicity Scale.

ABSTRACT: The interaction between amino acids (AAs) and hydration water is fundamental to protein folding and protein-protein interactions. Here, we proposed a hydrophobicity scale for AAs based on their computed free energetic cost of dewetting. This metric captures both entropic and enthalpic contributions of AA-water interactions and allows a systematic and intuitive classification of AAs. Using indirect umbrella sampling (INDUS), we rank individual AAs based on the relative magnitude of their dewetting free energies, from lowest (most hydrophobic) to highest (most hydrophilic). This new hydrophobicity scale is a starting point to evaluate different elements of water hydration behavior, and we focus here on the water structure and translational diffusivity of the hydration waters. While the latte

SUBMITTER: Najafi S 

PROVIDER: S-EPMC11848916 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature