Unfolding of protein using MoS2/SnS2heterostructure for nanopore-based sequencing.

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/SnS2heterostructures 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/SnS2heterostructure, it was found that the strong binding of protein to SnS2nanostripe 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 SnS2nanostripe. 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.

Navigated Delivery of Peptide to the Nanopore Using In-Plane Heterostructures of MoS2 and SnS2 for Protein Sequencing.

The impressive success of DNA sequencing using nanopores makes it possible to realize nanopore based protein sequencing. Well-controlled capture and linear movement of the protein are essential for accurate nanopore protein sequencing. Here, by taking advantage of different binding affinities of protein to two isomorphic materials, we theoretically designed a heterostructual platform for delivering the unfolded peptide to the nanopore sensing region. Due to the stronger binding between the peptide and SnS2 compared to MoS2, the peptide would adsorb to the SnS2 nanostripe and keep its threadlike conformation in the MoS2/SnS2/MoS2 heterostructure. Through switching the direction of the applied electric field in real time, the peptide was strategically driven to move along the designed path to the target nanopore. The ionic current blockades were also found to be different as the compositions of the peptide were changed, indicating the possibility for differentiating different peptides using this platform.