2.5. The molecular mechanics-generalized Born surface area (MM/GBSA) continuum solvation calculations

The MM/GBSA was used for calculating the binding free energies of studied compounds [⁵²]. Hou et al. in their succeeding studies represented that re-scoring by MM/GBSA is an effective procedure to improve the predictions of docking methods [⁵³]. As our aim was to propose novel compounds as NF-κB inhibitors in a relatively efficient and inexpensive technique, MM/GBSA approach was preferred [⁵⁴]. The MM/GBSA tool was conducted in this study using Schrodinger's Prime module [⁴⁸]. 100 trajectory frames were used to calculate the MM/GBSA from short (1 ns) MD simulations and 2000 trajectory frames were considered from the 50 ns (long) MD simulations. More details about the simulation protocol can be found in our previous studies [^{37,[55], [56], [57]}].

The study's full methodology is summarized in Scheme 1 .

The study's computational approach for screening libraries for the purpose of identifying drug-like molecules with potential anti-inflammatory activity.