Molecular Dynamics Study of FRET-Enabled Carbon Quantum Dot–Gold Nanoparticle Composites for Abasic DNA Detection

Abstract

Abasic sites, which result from spontaneous base loss or enzymatic cleavage, are critical biomarkers of DNA damage and genomic instability. Their sensitive detection is essential for understanding DNA repair processes and for advancing diagnostic biosensors. In this study, we employ molecular dynamics (MD) simulations to investigate the structural, energetic, and binding characteristics of a fluorescence resonance energy transfer (FRET)-enabled nanocomposite composed of nitrogen-doped carbon quantum dots (N-CQDs) and cysteamine-capped gold nanoparticles (Cyst/AuNPs) for a simple DNA detection. FRET, a distance-dependent nonradiative energy transfer between a fluorescent donor and an acceptor, serves as the readout mechanism for sensing events. Structural analyses revealed that N-CQDs possess highly accessible and stable functional groups that facilitate effective biomolecular interactions. Adsorption studies showed that normal DNA exhibits stronger binding to Cyst/AuNPs than abasic DNA, thereby suppressing FRET by preventing nanoparticle proximity. In contrast, the cleavage of abasic DNA by apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme in the base excision repair pathway, reduces the DNA affinity for AuNPs, allowing N-CQDs to approach and activate FRET, leading to fluorescence quenching. The distinct binding modes, predominantly driven by electrostatic and hydrogen-bonding interactions, highlight a DNA-length-dependent mechanism that modulates nanoparticle rearrangement and FRET efficiency. These findings provide mechanistic insights at the molecular level and establish foundational design principles for the development of sensitive and selective biosensors for the detection of DNA lesion, with potential applications in disease diagnostics and therapeutic monitoring.