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

Neurol Sci. 2018 Aug;39(8):1361-1374. doi: 10.1007/s10072-018-3430-2. Epub 2018 May 22.

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.

Keywords: Alzheimer’s disease; CASS4; Dynamic simulation; Molecular docking; PTK2.

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Alzheimer Disease / metabolism*
  • Animals
  • Binding Sites
  • Female
  • Focal Adhesion Kinase 1 / chemistry
  • Focal Adhesion Kinase 1 / metabolism*
  • Humans
  • Male
  • Molecular Docking Simulation*
  • Nonlinear Dynamics*
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Signal Transduction

Substances

  • Adaptor Proteins, Signal Transducing
  • CASS4 protein, human
  • Focal Adhesion Kinase 1