Structural insights and computational molecular docking to explore novel therapeutic drug targets of STAT3

Abstract

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor, that contains a DNA-binding domain, N-terminal domain, and SH2 domain. The dysregulation of STAT3 activity has been associated with various diseases, such as chronic inflammation and autoimmune disorders. In cancer, STAT3 is often constitutively activated and promotes tumor cell survival, proliferation, and immune evasion. Various bioinformatics approaches were employed to predict the 3D structure of STAT3, followed by a comprehensive evaluation of the predicted model. 3D predicted structure of the target protein revealed an overall quality factor of 94. 45%. It was also observed through the Ramachandran plot that 1.26% residues of the predicted structure of STAT3 were present in the outlier region of the protein structure. Computational docking studies were done to identify the novel drug targets against STAT3. The screened compound via high throughput virtual screening may have the potential to regulate the activity of STAT3. The lowest binding energy of -8.7 Kcal/mol was observed. His-457, Tyr-456, Lys-488, Pro-487, Gln-326, Leu-459, Lys-244, Gln-247 conserved residues were observed. The structural insight and functional determination of STAT3 depend on the identification of the potent binding domain in protein 3D structure.