Multiscale Theoretical Calculations Drive Mechanism Analysis and Application Expansion of Nanopore Detection

Abstract

Nanopore detection technology has broad application prospects in DNA, protein, and glycan sequencing, as well as in the highly sensitive detection and identification of bio-molecules. However, precise analysis of the structure-function relationship and targeted optimization of device performance remain key bottlenecks restricting further development. Computational simulations can not only explain and verify experimental phenomena but also potentially guide experimental design, shorten the research cycle, and reduce research costs. Therefore, this review comprehensively summarizes the application of multiscale computational calculations in nanopore systems. By incorporating quantum mechanics calculations, molecular docking, molecular dynamics simulations, and finite element analysis, we aim to provide theoretical support for addressing the aforementioned bottlenecks. Among these methods, atomic-scale calculations enable the precise characterization of molecular conformations and intermolecular interactions, thereby clarifying the nanopores’ microscale recognition mechanisms. Mesoscale simulations can trace the analyte translocation dynamics across nanopores, revealing inherent regulatory principles. Macroscale models effectively simulate the hydrodynamic behaviors of nanopore devices. In summary, the synergistic application of multiscale computational simulations establishes theoretical foundation for improving nanopore sensor performance. Furthermore, we discuss the challenges and future trends associated with the synergistic integration of computational simulations, aiming to provide valuable insights for researchers active in computational chemistry and nanopore-based fields.