Virtual structure-based docking and molecular dynamics of FDA-approved drugs for the identification of potential IKKB inhibitors possessing dopaminergic activity in Alzheimer’s disease

Abstract In Alzheimer's disease (AD), neuroinflammation is detrimental in causing neurodegeneration. the central nervous system, inhibitor of nuclear factor kappa B kinase subunit beta (IKK2/IKKβ/IKKB/IKBKB) signaling linked to neuroinflammation-mediated learning and memory deficits through canonical pathway, while dopamine agonists have been known reverse such effects. Our silico analysis predicted if dopaminergic could IKKB inhibitory actions, ameliorate neuroinflammation-associated deficits. Here, FDA-approved Zinc 15 database was screened with (PDB ID 4KIK). Potential molecules inhibition were identified docking, which also possessed activity. Molecular mechanics—generalized Born surface area (MMGBSA), induced fit docking (IFD) molecular dynamic (MD) studies 100 ns simulation time done. Apomorphine rotigotine showed greater non-bonding bonding interactions amino acids as compared Aripiprazole studies. The IFD improved IKKB. MMGBSA scores indicated that complex binding free energies favorable, MD an acceptable root mean square deviation between protein ligands. protein–ligand hydrogen bonds, water salt bridges necessary for inhibition, well solvent system stability. On contact map, varying color band intensities represented ligand’s ability bind acids. Dopamine apomorphine, rotigotine, aripiprazole inhibit system. Graphical