LAUSR

Excitotoxicity, depletion of energy metabolites, and ionic imbalance are the major factors involved in neurodegeneration mediated through excitatory amino acid transporter‐2 (EAAT‐2) dysfunction in ischemic insult. Recent studies have revealed that ceftriaxone expresses EAAT‐2 via nuclear transcription factor kappa‐B (NF‐kB) signaling pathway, stimulation of EAAT‐2 expression in the ischemic, and excitotoxic conditions that could provide potential benefits to control neurodegeneration. In this study, we have predicted the in silico model for interaction between NF‐kB and EAAT‐2 promoter region to rule out the conformational changes for the expression of EAAT‐2 protein. Using homology‐built model of NF‐kB, we identified ceftriaxone‐induced conformational changes in gene locus −272 of DNA where NF‐kB binding with EAAT‐2 promoter region through protein−DNA docking calculation. The interaction profile and conformational dynamics occurred between ceftriaxone predocked and postdocked conformations of NF‐kB with DNA employing HADDOCK 2.2 web server followed by 250 ns long all atom explicit solvent molecular dynamics simulations. Both the protein and DNA exhibited modest conformational changes with respect to HADDOCK score, energy terms (desolvation energy [Edesolv]), van der waal energy (Evdw), electrostatic energy (Eelec), restraints energy (Eair), buried surface area, root mean square deviation, RMSF, radius of gyration, total hydrogen bonds when ceftriaxone pre‐ and postdocked NF‐kB conformations were bound to DNA. Hence, the conformational changes in the C‐terminal domain could be the reason for EAAT‐2 expression through ceftriaxone specific binding pocket of −272 of DNA.