Unfolding of protein using MoS2/SnS2 heterostructure for nanopore-based sequencing

Abstract

Protein sequencing is crucial for understanding the complex mechanisms driving biological functions. However, proteins are usually folded in their native state and the mechanism of fast protein conformation transitions still remains unclear, which make protein sequencing challenging. Molecular dynamics simulations with accurate force field are now able to observe the entire folding/unfolding process, providing valuable insights into protein folding mechanisms. Given that proteins can be unfolded, nanopore technology shows great potential for protein sequencing. In this study, we proposed to use MoS2/SnS2 heterostructures to firstly unfold proteins and then detect them by a nanopore in the heterostructural membrane. All-atom molecular dynamics simulations performed in this work provided rich atomic-level information for a comprehensive understanding of protein unfolding process and mechanism on the MoS2/SnS2 heterostructure, it was found that the strong binding of protein to SnS2 nanostripe and hydrogen bond breaking were the main reasons for unfolding the protein on the heterostructure. After the protein was fully unfolded, it was restrained on the nanostripe because of the affinity of protein to the SnS2 nanostripe. Thus by integrating the proposed unfolding technique with nanopore technology, detection of linear unfolded peptide was realized in this work, allowing for the identification of protein components, which is essential for sequencing proteins in the near future.