One-Dimensional Molecular Coordinate Orders Amino Acids across Water-Mediated Processes

Abstract

Amino acid behavior in water-mediated processes is not well captured by hydrophobicity or side-chain class alone, because residues with similar hydropathy can differ in charge localization, geometry, surface exposure, and hydration response. The objective of this study is to determine whether integrating complementary molecular representations can reveal a chemically interpretable molecular coordinate that organizes amino acid behavior across distinct water-mediated processes. We fused electronic-, structural-, and solvation-level representations into a similarity network and embedded it spectrally to obtain a one-dimensional coordinate, ZF, which captures coupled variation in electrostatics-, geometry-, and hydration-related features. Across gas hydrate formation, ice recrystallization inhibition, and CaCO3 crystallization, ZF provides a consistent residue-level coordinate and captures interaction trends that differ in direction from those described by the Kyte–Doolittle hydropathy scale in the latter two systems.