A Reductionist Molecular Dynamics Framework for Identifying Molecular Descriptors of Hydration at Solid–Liquid Biomaterial Interfaces

In synthetic polymer-based biomaterials, interfacial hydration plays a crucial role in biological interactions with proteins and cells. Although a wide range of polymers, including zwitterionic and non-ionic types, are used as biomaterials, the molecular principles by which their chemical structures influence interfacial hydration and suppress nonspecific protein adsorption remain unclear, hindering the discovery of novel biomaterials. In this study, we developed a reductionist bulk solid–liquid molecular dynamics (MD) framework that deliberately excludes system-specific factors such as polymer stereoregularity. Non-ionic, amino-acid-based zwitterionic, betaine-based zwitterionic, and highly polar polymers were evaluated using established hydrogen-bond (HB) analyses. HB distance and angle distributions, HB number, radial distribution functions (RDF), HB lifetimes, and HB dissociation–reformation dynamics were analyzed to characterize the spatial and temporal behavior of interfacial hydration. These analyses revealed distinct hydration profiles among the polymer systems. The rkf/rkb ratio was examined as a candidate descriptor characterizing the relative timescales of HB dissociation and reformation. Although polymer-dependent differences were observed under the present simulation conditions, their quantitative convergence and relationship with biological performance remain to be established. The ratio may therefore provide a useful starting point for future studies aimed at developing hydration-related molecular descriptors for AI/ML-assisted screening. Overall, the proposed reductionist framework provides a practical strategy for identifying hydration-related molecular descriptors using established MD analyses.