Molecular dynamics and free energy analysis of curcumin binding near the DNA-recognition interface of NF-κB

Curcumin, a natural polyphenolic compound derived from Curcuma longa, is widely reported to modulate NF-κB signaling, primarily through indirect effects on upstream regulatory pathways. However, residue-level information on possible curcumin association near structurally relevant regions of NF-κB remains limited. Here, we investigated the predicted binding behavior of curcumin near the DNA-recognition region of the NF-κB p50 homodimer using molecular docking, 100 ns all-atom molecular dynamics simulation, and MM-PBSA free-energy analysis. Docking with the p50 homodimer model derived from PDB ID 1SVC identified a preferred pose near the Rel Homology Domain with an AutoDock Vina score of − 6.0 kcal/mol. Molecular dynamics simulations showed that the curcumin-bound model maintained persistent local contacts and exhibited reduced residue-level fluctuations near the predicted binding region. The complex showed a compact structural profile, with Radius of gyration (R_g) values in the range of 2.50–2.60 nm, and lower solvent-accessible surface area relative to the apo model. MM-PBSA analysis indicated a favorable relative binding free energy dominated by van der Waals and electrostatic contributions. These findings provide a computational residue-level characterization of curcumin association near the NF-κB p50 DNA-recognition region.