Abstract

IN SILICO STUDY TO EVALUATE THE MOLECULAR INTERACTIONS BETWEEN SOMATOSTATIN AND ITS RECEPTOR SSTR5

Sneha Manaswita, Amand Bhaskar, Raju Poddar, Kunal Mukhopadhyay,Manish Kumar*

ABSTRACT

Somatostatin is a tetradecapeptide which inhibits the secretion of pituitary and pancreatic hormones like growth hormone, insulin and glucagon. Failure of this inhibitory effect of somatostatin may lead to abnormalities like acromegaly, pancreatic and neuroendocrine tumors. The present study was designed to develop analogues having high binding affinity for the receptor that may help in the treatment of acromegaly and onset of large neuroendocrine tumors. As there is no structural information available for somatostatin receptor 5, homology modeling was performed with human dopamine receptor D3 (3PBL) as the template using the software MODELER9v8. To study the molecular interaction the generated model of the receptor was docked with somatostatin-14 after energy minimization. The results obtained after docking indicated formation of a stable complex with strong binding affinity between somatostatin-14 and somatostatin receptor 5. It was observed that the amino acid residues lying in transmembrane helix 2, 3and 7 are involved in this interaction and the predicted residues responsible for binding are Leu96, Ser167, Leu168, Met170, Phe177 and Arg248.The molecular interaction study between somatostatin and its receptor may help in the elucidation of structural domains and development of novel analogues with higher binding affinity and new drug combination therapies for the treatment of acromegaly and large neuroendocrine tumors.

Keywords: Somatostatin, G Protein Coupled Receptor, Acromeagaly, Docking, Molecular Interaction.