Structure, molecular dynamics simulation, and docking studies of Dictyostelium discoideum and human STRAPs

• Published in: Journal of cellular biochemistry 2018-09, Vol.119 (9), p.7177-7191
• Main Authors: Kumar, Rakesh, Saran, Shweta
• Format: Article
• Language: English
• Subjects: Carcinoma; Cell proliferation; Computer simulation; Dictyostelium discoideum; docking; Dynamic structural analysis; essential dynamics; Homology; In vivo methods and tests; I‐TASSER; Kinases; Lungs; MM‐PBSA; Molecular docking; Molecular dynamics; molecular dynamics simulation; Molecular structure; principle component analysis; Protein interaction; Protein-serine/threonine kinase; Proteins; Signal transduction; Signaling; Smad7 protein; STRAP; Straps; Target recognition; Therapeutic applications
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.26840

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. Identification of a novel drug target for STRAP protein. Analyzed the participation of STRAP in protein‐protein interaction. We propose that Dictyostelium discoideum could be used as a model system to understand the biology and chemistry of STRAP protein.