Probing nanopores: molecular dynamics insights into the mechanisms of DNA and protein translocation through solid-state and biological nanopores

Abstract

Nanopore sequencing technology has revolutionized single-molecule analysis through its unique capability to detect and characterize individual biomolecules with unprecedented precision. This perspective provides a comprehensive analysis of molecular dynamics (MD) simulations in nanopore research, with particular emphasis on comparing molecular transport mechanisms between biological and solid-state platforms. We first examine how MD simulations at atomic resolution reveal distinct characteristics: biological nanopores exhibit sophisticated molecular recognition through specific amino acid interactions, while solid-state nanopores demonstrate advantages in structural stability and geometric control. Through detailed analysis of simulation methodologies and their applications, we show how computational approaches have advanced our understanding of critical phenomena such as ion selectivity, conformational dynamics, and surface effects in both nanopore types. Despite computational challenges including limited simulation timescales and force field accuracy constraints, recent advances in high-performance computing and artificial intelligence integration have significantly improved simulation capabilities. By synthesizing perspectives from physics, chemistry, biology, and computational science, this perspective provides both theoretical insights and practical guidelines for developing next-generation nanopore platforms. The integration of computational and experimental approaches discussed here offers promising directions for advancing nanopore technology in applications ranging from DNA/RNA sequencing and protein post-translational modification analysis to disease diagnosis and drug screening.