Molecular Dynamics of A Biglycan-Rosmarinic Acid Complex with Focal Adhesion Kinase for Possible Arrest of Metastasis in Non-Small Cell Lung Cancer (NSCLC): An In- Silico Study

  • Hyacinth Highland Department of Zoology, Biomedical Technology and Human Genetics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India
  • Monica Thakur Department of Biochemistry, School of sciences, Gujarat University, Ahmedabad-380009, Gujarat, India
  • Pujan Pandya Department of Botany, Bioinformatics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India
  • Archana Mankad Department of Botany, Bioinformatics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India
  • Linz-Buoy George Department of Zoology, Biomedical Technology and Human Genetics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

Abstract

Background: Non-small cell lung cancer (NSCLC) is the major cause of mortality all over the world. Significant increase of biglycan is seen in the lung cancer cells when compared with the normal cells. It promotes tumor invasion and metastasis by activating Focal Adhesion Kinase (FAK) signaling pathway. The increased FAK activity may contribute to the metastatic potential of malignant tumors. This study was carried out to establish binding interactions of some selected phytocomponents against biglycan for the possible arrest of metastasis.


Methods: Protein-ligand interaction studies were performed using 30 natural compounds from different culinary herbs having potential therapeutic role against the target protein biglycan (BGN).


Molegro Virtual Docker (v 5.0) was used as docking tool to evaluate the effectiveness of selected phytocomponents based upon the interaction with the protein’s active site residues with minimal binding energy. Protein-protein docking was performed to observe the interaction of BGN and FAK using Hex (v 8.0.0). Molecular dynamics (10 ns) of BGN-RA-FAK and FAK-RA-BGN was performed in Yasara structure (v 17.8.15) which showed stability of the structure in terms of RMSD values.


Results: Molecular docking analysis revealed the selectivity of Rosmarinic acid (RA) towards BGN and FAK. Molecular dynamics trajectory of BGN-RA-FAK and FAK-RA-BGN complexes showed the stability of structure in terms of Time vs Energy and Time vs RMSD values and revealed that binding of RA to BGN will block the interaction of FAK.


Conclusions: Hence, investigating the binding interactions of BGN-RA-FAK complex may turn out to be helpful in arresting metastasis in NSCLC.


Keywords: Non-small cell lung cancer, Biglycan, Focal adhesion kinase, Phytocomponents, Molecular Docking, Molecular Dynamics

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Author Biographies

Hyacinth Highland, Department of Zoology, Biomedical Technology and Human Genetics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

Dr. Hyacinth Highland, Ph.D

Department of Zoology, Biomedical Technology and Human Genetics,     

School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

Monica Thakur, Department of Biochemistry, School of sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

Ms. Monica Thakur, M.Sc.

Department of Biochemistry, School of sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

Pujan Pandya, Department of Botany, Bioinformatics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

Ms. Pujan Pandya, M.Sc.

Department of Botany, Bioinformatics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

Archana Mankad, Department of Botany, Bioinformatics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

Dr. Archana Mankad, Ph.D

Department of Botany, Bioinformatics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

Linz-Buoy George, Department of Zoology, Biomedical Technology and Human Genetics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

Dr. Linz-Buoy George, Ph.D.

Department of Zoology, Biomedical Technology and Human Genetics, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India

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How to Cite
Highland, H., Thakur, M., Pandya, P., Mankad, A., & George, L.-B. (2019). Molecular Dynamics of A Biglycan-Rosmarinic Acid Complex with Focal Adhesion Kinase for Possible Arrest of Metastasis in Non-Small Cell Lung Cancer (NSCLC): An In- Silico Study. Journal of Drug Delivery and Therapeutics, 9(4-A), 159-166. https://doi.org/10.22270/jddt.v9i4-A.3382