Structure, molecular dynamics simulation, and docking studies of Dictyostelium discoideum and human STRAPs.
Rakesh KumarShweta SaranPublished in: Journal of cellular biochemistry (2018)
The Serine Threonine kinase Receptor Associated Protein (STRAP) is a WD40 containing protein that provides a platform for protein interactions during cell proliferation and development. Overexpression and misregulation of STRAP contributes to various carcinomas that are now recognized as therapeutic targets especially for colorectal and lung cancers. The present study was undertaken to find an effective drug against this molecule using a simple system like Dictyostelium discoideum; which shares close homology to humans. Using techniques like structural modeling, molecular dynamics (MD) simulation and molecular docking, we found similar structure and dynamic behaviors in both, except for the presence of dissimilar numbers of β-sheets and loop segments. We identified a novel and potential drug targeted to STRAP. The results obtained allow us to use Dictyostelium as a model system for further in vivo studies. Finally, the results of protein-protein interactions using molecular docking and essential dynamics studies show STRAP to participate in TGF-β signaling in humans. Further, we show some structural units that govern the interaction of TGFβ-RI with STRAP and Smad7 proteins in TGF-β signaling pathway. In conclusion, we propose that D. discoideum can be used for enhancing our knowledge about STRAP protein.
Keyphrases
- molecular docking
- molecular dynamics simulations
- molecular dynamics
- transforming growth factor
- cell proliferation
- protein protein
- signaling pathway
- epithelial mesenchymal transition
- density functional theory
- case control
- protein kinase
- binding protein
- endothelial cells
- amino acid
- pi k akt
- emergency department
- high grade
- young adults
- drug induced
- high throughput
- adverse drug
- human health
- drug delivery
- risk assessment
- childhood cancer