Molecular Mechanisms of Spontaneous Peptide Translocation through BC3/C3N Heterostructure Nanopores: A Molecular Dynamics Study

Solid-state nanopore (SSN) sequencing has emerged as a revolutionary technique in genetic and proteomic analysis, offering low costs and long read-lengths. However, traditional SSN sequencing, which relies on an electric field to drive biomolecules, faces challenges in translocating nonuniformly charged proteins, limiting its application in single-molecule protein sequencing. In this work, molecular dynamics (MD) simulations were employed to investigate peptide translocation across a BC3/C3N van der Waals (vdW) heterostructure nanopore in the absence of external forces. Our results revealed that the peptide spontaneously translocates from the BC3 surface to the C3N surface due to stronger binding on the latter. However, the translocation is temporarily impeded by aromatic Phe residues, which experience strong π–π interactions with nanosurfaces, creating significant energy barriers for Phe desorption. These findings clarify the molecular-scale interactions that govern peptide motion across the BC3/C3N heterostructure interface and reveal how asymmetric adsorption energetics enable spontaneous, directional transport. Rather than assessing sequencing feasibility, this study provides mechanistic insights into heterostructure-mediated peptide motion and establishes a conceptual framework for future investigations of nanopore-based biomolecule manipulation.