Structural Analysis of RNA-Binding Protein EWSR1 Involved in Ewing’s Sarcoma Through Domain Assembly and Conformational Molecular Dynamics Studies

Abstract

Proteins are active players in different sarcomas through actively participating in downstream signaling pathways. EWS RNA-Binding Protein 1 (EWSR1) is considered as good therapeutic target for treatment of Ewing’s sarcoma. In current study, comparative modeling approach was employed to predict the structural models of three different domains of EWSR1 and Domain Enhanced MOdeling (DEMO) server was used to compose the predicted models of three domains. Furthermore, RNA motifs binding to EWSR1 were predicted and the 3D model of RNA bound to EWSR1 was built by using MC-Fold. The conformational interactions between EWSR1 and RNA were studied with HNADOCK. Moreover, MD simulations were performed to check the stability of EWSR1-RNA complex by computing RMSD, RMSF, Rg, and SASA graphs. Based on computational assessments, it has been concluded that certain structural and dynamical features of EWSR1-RNA complex could be used as a target in future development of drugs against Ewing’s sarcoma.