Hydrophobicity-Governed Protein Adsorption on Poly(ω-methoxyalkyl acrylate) Surfaces: A Coarse-Grained Molecular Dynamics Study

Polymeric materials are widely used in medical devices, where their interactions with proteins play a critical role in determining biocompatibility. To better understand and predict these interactions, we extend the coarse-grained force field (FF), SPICA, to simulate protein adsorption on poly(ω-methoxyalkyl acrylate) (PMC_<i>x</i>A) and poly(<i>n</i>-butyl acrylate) (PBA) surfaces. Notably, poly(2-methoxyethyl acrylate) (PMEA), a member of PMC_<i>x</i>A family, is approved by the U.S. Food and Drug Administration for clinical applications. Our polymer FF was parametrized using the physical properties─density, interfacial tension, and hydration free energy─of small-molecule analogs representing the monomer units. Protein-polymer interactions were further calibrated using adsorption free energies of amino acid side-chain analogs on polymer-based monolayers. The developed SPICA-FF accurately reproduces both bulk polymer properties and protein adsorption behaviors in agreement with experimental and atomistic simulation data. Our simulations show that PBA strongly attracts water-soluble globular proteins, while PMEA resists adsorption when proteins retain their native structures. For PMC_<i>x</i>A variants, protein adsorption correlates linearly with both surface water contact angle and the free energy of cavity formation at the interface, highlighting surface hydrophobicity─particularly the number of methylene units in the polymer side chains─as a key determinant. This work offers a validated framework for studying protein-polymer interactions at a coarse-grained level, enabling more efficient screening and design of polymer surfaces for medical applications. It highlights the significance of polymer surface chemistry in determining protein behavior, offering valuable insights for the rational design of biocompatible materials.