Using nanopores for the single-molecule sequencing of proteins – similar to nanopore-based sequencing of DNA – faces multiple challenges, including unfolding of the complex tertiary structure of the proteins and enforcing their unidirectional translocation through nanopores. Here, we combine molecular dynamics (MD) simulations with single-molecule experiments to investigate the utility of SDS (Sodium Dodecyl Sulfate) to unfold proteins for solid-state nanopore translocation, while simultaneously endowing them with a stronger electrical charge. Our simulations and experiments probe that SDS-treated proteins show considerable loss of protein structure during the nanopore translocation. Moreover, SDS-treated proteins translocate through the nanopore in the direction prescribed by the electrophoretic force fue to the negative charge impaired by SDS. In summary, our results suggest that SDS causes protein unfolding while facilitating protein translocation in the direction of the electrophoretic force, both characteristics could bring great advantages for future protein sequencing applications using solid-state nanopores.

Molecular dynamics simulations reveal how anionic surfactant SDS and heat unfold full-length proteins.