Exploring the mechanistic insights of Cas scaffolding protein family member 4 with protein tyrosine kinase 2 in Alzheimer’s disease by evaluating protein interactions through molecular docking and dynamic simulations

Mubashir Hassan, Saba Shahzadi, Hany Alashwal, Nazar Zaki, Sung Yum Seo, Ahmed A. Moustafa

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Cas scaffolding protein family member 4 and protein tyrosine kinase 2 are signaling proteins, which are involved in neuritic plaques burden, neurofibrillary tangles, and disruption of synaptic connections in Alzheimer’s disease. In the current study, a computational approach was employed to explore the active binding sites of Cas scaffolding protein family member 4 and protein tyrosine kinase 2 proteins and their significant role in the activation of downstream signaling pathways. Sequential and structural analyses were performed on Cas scaffolding protein family member 4 and protein tyrosine kinase 2 to identify their core active binding sites. Molecular docking servers were used to predict the common interacting residues in both Cas scaffolding protein family member 4 and protein tyrosine kinase 2 and their involvement in Alzheimer’s disease-mediated pathways. Furthermore, the results from molecular dynamic simulation experiment show the stability of targeted proteins. In addition, the generated root mean square deviations and fluctuations, solvent-accessible surface area, and gyration graphs also depict their backbone stability and compactness, respectively. A better understanding of CAS and their interconnected protein signaling cascade may help provide a treatment for Alzheimer’s disease. Further, Cas scaffolding protein family member 4 could be used as a novel target for the treatment of Alzheimer’s disease by inhibiting the protein tyrosine kinase 2 pathway.

Original languageEnglish
Pages (from-to)1361-1374
Number of pages14
JournalNeurological Sciences
Volume39
Issue number8
DOIs
Publication statusPublished - Aug 1 2018

Keywords

  • Alzheimer’s disease
  • CASS4
  • Dynamic simulation
  • Molecular docking
  • PTK2

ASJC Scopus subject areas

  • Dermatology
  • Clinical Neurology
  • Psychiatry and Mental health

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