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bioRxiv · 10.1101/2025.05.02.651893

All-Atom Modeling and Simulation of Biopolymer Interface: Dual Role of Antifouling Polymer Brushes

Kim, S.·Yang, Z.·Jakowski, J.·Ganesh, P.·Retterer, S.·Carrillo, J.-M.
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Abstract

Antifouling polymers are highly valuable in a variety of applications, including antiviral coatings, targeted drug delivery, and marine coatings, where preventing unwanted protein adsorption is critical. Although extensive experimental studies have characterized polymer-protein interactions, computational studies remain limited due to the inherent difficulty of modeling and integrating these distinct components within a unified system. This study presents molecular modeling and simulation of polyelectrolyte and polyzwitterionic brushes--poly(dimethylaminoethyl methacrylate) (PDMAEMA), poly(2-(N-oxide-N,N-dimethylamino)ethyl methacrylate) (PNOMA), and poly(2-(N-3-sulfopropyl-N,N-dimethylammonium)ethyl methacrylate) (PSBMA)--grafted onto -quartz substrates in the presence of lysozyme protein. The brush models were developed to closely replicate experimentally synthesized brush samples and to provide detailed insights into structural and dynamical changes at the molecular level during protein adsorption. Using steered molecular dynamics simulations, we show that the PSBMA brush, due to its high local density, exhibits the greatest resistance to protein insertion. C root-mean-square deviation and interaction patterns analyses further reveal that PSBMA also induces the most significant destabilization of lysozyme, while PDMAEMA brush enhances protein stability through ion-mediated interactions. The PNOMA brush, while requiring the lowest force for protein adsorption, induces greater protein destabilization than the PDMAEMA brush primarily due to electrostatic repulsion caused by a short carbon spacer length. To the best of our knowledge, this study presents the first comprehensive and realistic model system--comprising nanomaterials, polymers, and proteins, specifically antifouling polyzwitterions and polyelectrolytes grafted onto -quartz substrates via linkers. These findings highlight the dual role of antifouling polymer brushes: resisting protein adsorption and modulating protein structural dynamics, offering valuable insights for the rational design of next-generation antifouling materials. TOC GRAPHICS O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/651893v1_ufig1.gif" ALT="Figure 1"> View larger version (72K): org.highwire.dtl.DTLVardef@9620b8org.highwire.dtl.DTLVardef@3e395dorg.highwire.dtl.DTLVardef@1282169org.highwire.dtl.DTLVardef@1a997f7_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Kim, S., Yang, Z., Jakowski, J., Ganesh, P., Retterer, S., Carrillo, J.-M.. 2025-05-06. All-Atom Modeling and Simulation of Biopolymer Interface: Dual Role of Antifouling Polymer Brushes. https://doi.org/10.1101/2025.05.02.651893

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