A universal "Divide-and-conquer, precise reconstruction" strategy: Multiscale simulation-guided high-fidelity...

The high-fidelity encapsulation and controlled release of natural aromas remain significant challenges in flavor science due to the compositional complexity of essential oils and heterogeneous host-guest interactions in conventional co-inclusion systems. Using rose aroma as a representative model, this study presents a "divide-and-conquer, precise reconstruction" strategy that integrates multiscale simulation with experimental validation. Seven key aroma-active compounds were screened through GC-MS combined with odor activity value (OAV) analysis. Their host-guest interactions with β-cyclodextrin (β-CD) were subsequently investigated using molecular docking, molecular dynamics simulations, and MM/PBSA free-energy calculations. The results suggest that hydrophobic interactions dominate the complexation process, and the calculated binding free energies (ΔG_bind: -1.67 to -7.34 kcal/mol) show semi-quantitative consistency with experimentally observed encapsulation behavior and release trends. Individual inclusion complexes (ICs) exhibited markedly improved thermal stability, with decomposition onset temperatures increasing by more than 150 °C compared with free compounds. Successful complex formation was confirmed through FTIR, XRD, and ¹H NMR characterization. Release kinetics analysis revealed compound-specific release behaviors governed by interaction strength and molecular compatibility with β-CD. Based on these differentiated release profiles, physical blending of individually prepared ICs enabled reconstruction of a headspace aroma composition highly consistent with that of the original rose extract, outperforming conventional co-inclusion under identical conditions. Beyond demonstrating a successful case for rose aroma, this work establishes a simulation-guided design framework integrating key component screening, interaction prediction, precise preparation, and release-controlled reconstruction. The proposed methodology provides a rational strategy that can potentially be extended to other complex natural aroma systems for the development of advanced flavor delivery system.