Spacing Over Sequence: Design Considerations for Polystyrene-binding Polypeptides

Plastic-binding polypeptides have emerging applications in biosensor design, materials functionalization, and nanoplastic capture, and the rational design of new sequences requires the development of structural and sequence-based design principles. Here, we demonstrate a computational workflow combining atomistic molecular dynamics simulations and enhanced sampling to evaluate polypeptide binding to polystyrene, a common commodity plastic. We investigate two candidate sequences previously proposed as polystyrene binders, both enriched in either aromatic or cationic residues expected to interact with polystyrene's aromatic rings. We find that the two sequences bind stably through apparent π-stacking and cation-π interactions. These binding modalities rely on proper residue spacing; not all cationic residues on a polypeptide bind unless separated by linking residues as demonstrated by our “arginine claw” motif. We also determine that the presence of the polypeptide does shield the polystyrene from contacts with solvent, though it does not promote further self-collapse of the oligomer. Our analysis demonstrates how sequence composition coupled with sequence orientation enables multiple binding modalities, determining motifs such as the “arginine claw” and aromatic ring distribution that can be leveraged in future polypeptide design.