Unravelling amino acid–graphene interactions: insights from polarizable force field simulations

Abstract

Understanding the interactions between amino acids and graphene surfaces is crucial for advancing applications in biosensing, drug delivery, and nanobiotechnology. In this study, we employ both Drude polarizable and additive force field molecular dynamics simulations to systematically investigate the adsorption behavior and binding energetics of all twenty proteinogenic amino acids on multilayer graphene in an aqueous solution. Adaptive Biasing Force (ABF) simulations reveal that polarizable force fields capture significantly stronger and more nuanced binding affinities, particularly for charged and aromatic amino acids, compared to additive models. Our results highlight the critical role of electronic polarization in accurately describing anion–graphene and cation–graphene interactions, which are often underestimated by traditional additive force fields. Detailed analysis of the potential of mean force (PMF) profiles and binding free energies shows that side chain chemistry—especially for arginine, glutamate, aspartate, tryptophan, and tyrosine—strongly influences adsorption strength and conformational preferences. Secondary structure analysis demonstrates that polarizable simulations better reproduce experimentally observed changes in peptide helicity, β-sheet, and polyproline II conformations upon adsorption. These findings highlight the impact of homogeneous polarizable models for the description of bio–nano interfaces and provide new molecular-level insights into the structural and energetic landscape of amino acid adsorption on graphene.