Computational investigation of mechanistic insights of Aβ42 interactions against extracellular domain of nAChRα7 in Alzheimer's disease. (3rd July 2019)

• Record Type: Journal Article
• Authors: Hassan, Mubashir; Shahzadi, Saba; Raza, Hussain; Abbasi, Muhammad Athar; Alashwal, Hany; Zaki, Nazar; Moustafa, Ahmed A.; Seo, Sung-Yum
• Is Part Of: International journal of neuroscience. Volume 129:Number 7(2019)
• Page Start: 666
• Page End: 680
• Publication Date: 2019-07-03
• Subjects: Alzheimer's disease -- computational modelling -- molecular docking -- dynamic simulation -- Aβ42 -- nAChRα7; Nervous system -- Periodicals; 612.805
• DOI: 10.1080/00207454.2018.1543670
• Languages: English
• ISSNs: 0020-7454

Abstract

Abstract: Aim: Amyloid beta (Aβ) 1-42, which is a basic constituent of amyloid plaques, binds with extracellular transmembrane receptor nicotine acetylcholine receptor α7 (nAChRα7) in Alzheimer's disease. Materials and Methods: In the current study, a computational approach was employed to explore the active binding sites of nAChRα7 through Aβ 1–42 interactions and their involvement in the activation of downstream signalling pathways. Sequential and structural analyses were performed on the extracellular part of nAChRα7 to identify its core active binding site. Results: Results showed that a conserved residual pattern and well superimposed structures were observed in all nAChRs proteins. Molecular docking servers were used to predict the common interactive residues in nAChRα7 and Aβ1–42 proteins. The docking profile results showed some common interactive residues such as Glu22, Ala42 and Trp171 may consider as the active key player in the activation of downstream signalling pathways. Moreover, the signal communication and receiving efficacy of best-docked complexes was checked through DynOmic online server. Furthermore, the results from molecular dynamic simulation experiment showed the stability of nAChRα7. The generated root mean square deviations and fluctuations (RMSD/F), solvent accessible surface area (SASA) and radius of gyration (Rg) graphs of nAChRα7 also showed its backbone stability and compactness, respectively. Conclusion: Taken together, our predicted results intimated the structural insight on the molecular interactions of beta amyloid protein involved in the activation of nAChRα7 receptor. In future, a better understanding of nAChRα7 and their interconnected proteins signalling cascade may be consider as target to cure Alzheimer's disease.