In silico validation of human N-myc downstream-regulated gene 2 protein against Alzheimer's disease using molecular modeling, docking and dynamics studies

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ObjectivesThe human N-myc downstream-regulated gene 2 (hNDRG2) protein is mainly responsible for Alzheimer's disease (AD). It has 371 amino acid residues in their sequence. The 3dimensional (3D) structure of the complete sequence of this protein is still unknown. The present research computationally emphases to predict the 3D structure for the complete sequence of hNDRG2 protein and efficiency of this protein against AD was evaluated with synthetic and natural compounds using docking studies. Molecular dynamics (MD) study was performed to find the stability of the best interacted molecule. MethodsThe hNDRG2 protein was modeled using Modeller9v10. The lead compounds were retrieved from PubChem database. Docking studies were performed using AutoDock4.2. MD study was done by Macro model. ResultsThe modeled hNDRG2 protein was validated using Ramachandran plot and it showed the value of 90.8% in the most favored regions. From the results of docking studies, the interaction of modeled protein with synthetic tacrine showed the binding energy value of −4.44 kcal/mol and the interactions with 15 phytocompounds of Rosmarinus officinalis, a natural compound (+)-borneol showed the best binding energy value of −4.64 kcal/mol. The result of MD study determined that, the complex of modeled protein with (+)-borneol was stable at 2.2 ns. ConclusionsIn the above study, when the interaction of phytocompounds compared with synthetic tacrine, the natural compound (+)-borneol have showed good interaction with modeled protein and it is suggested to treat AD for avoiding the side effects of synthetic drugs.