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Computational structure and functional relationship of G protein-coupled receptor, a novel adhesion protein target for the treatment of triple negative breast cancer


Indiraleka Muthiah, Karthikeyan Rajendran*, Premnath Dhanaraj and Sugumari Vallinayagam  


Background: Adhesion G Protein-Coupled Receptor 116 (GPR116) is an orphan receptor known for the function and variety of extracellular signalling, cell- cell adhesion, angiogenesis and cell migration. Many studies have shown that different GPCRs are over expressed in several cancers. GPR116 could be a pharmacologically important drug target for triple negative breast cancer (TNBC), because previous studies have found that the knockdown of GPR116 results in suppression of cell migration and invasion. However no drugs targeting GPR116 were identified until now.

Objective: In this study, GPR116 is considered as a selective target for triple negative breast cancer treatment.

Methods: Computational molecular characterisation of GPR116 was carried out to identify crucial amino acids. In this regard Food and Drug Administration (FDA) approved breast cancer drugs were selected as ligands and performed molecular docking study with insilico protein structure of GPR116 receptor. Molecular dynamics simulations have been used to study structural and dynamic properties of highly interacted molecule Doxorubicin-GPR116 protein complex.

Results: The results reveal that Doxorubicin, Neratinib maleate, Epirubicin and Lapatinib Ditosylate has good hydrogen bonding interaction with GPR116 receptor protein binding site. Tyrosine 195 (Y 195), Cysteine 196 (C 196), Argenine (R 197) and Tryptophan 100 (W 100) are commonly found in majority of ligand target interaction, hence based on the computational studies active site selective amino acids might be crucial for functional properties. Further to confirm crucial amino acids, computational mutation studies were executed. Theoretical confirmatory structural properties changes supports to prove selective crucial amino acids play a significant role in ligand binding. Molecular dynamic simulation study results reveal that the interaction was stable throughout the MD simulation.

Conclusion: To the best of our prognosis, our results represent and strengthen to conform the list of crucial and essential amino acid . To investigate further in vitro/in vivo assay to confirm the active site in breast cancer functional receptor and crucial amino acid to confirm active drug molecular interaction.


GPR116, crucial amino acids, molecular modelling, docking, molecular simulation


Department of Biotechnology, Mepco Schlenk Engineering College, Sivakasi, Tamilnadu, Department of Biotechnology, Mepco Schlenk Engineering College, Sivakasi, Tamilnadu, Department of Biotechnology, School of Agriculture and Biosciences, Karunya Institute of Technology and science (Deemed to be University), Coimbatore 641114, Tamilnadu, Department of Biotechnology, Mepco Schlenk Engineering College, Sivakasi, Tamilnadu

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