Discovery of inhibitors for focal adhesion kinase (FAK): Molecular modeling study for combating cancer

  Nidhi Tripathi

Focal adhesion kinase (FAK) is a tyrosine kinase that controls the signals leading to invasion and metastasis and is involved in many aspects of the metastatic process including adhesion, migration, and invasion. It is known that FAK is activated from integrin and growth factor receptors by auto-phosphorylation followed by subsequent activation of other functional phosphorylation sites to advance the signals to downstream pathways, such as AKT. Based on these facts, FAK is thought to play a critical role in malignant behavior including proliferation, survival, and invasion. FAK is over expressed in many tumors, including those derived from the head and neck, colon, breast, prostate, liver, and thyroid. Inhibition of FAK signaling by over expression of dominant-negative fragments of FAK reduces invasion of glioblastomas and ovarian cancer cells. FAK therefore represents an important target for the development of anti-neoplastic and anti-metastatic drugs. We have attempted with the help of virtual screening and molecular docking approach using Lamarckian Genetic Algorithm to see the binding mode of extracts and compounds from the Rhizomes of Veratrum dahuricum. The study conducted involved virtual screening of nearly 115 molecules on basis of structure similarity of active molecules from roots of Veratrum dahuricum. Molecular docking using Lamarckian Genetic Algorithm was carried out for these ligands and the result gave binding energies which were in the range of -12.28 kcal/mol to -1.14 kcal/mol. The top 4 best docked protein were visualized using UCSF chimera which resulted in finding intricate atomic scale properties between ligand and active site of FAK, PBD ID- 2JKO. The top molecules then were run for in-silico ADMET and druglikeness properties showed promising results. Further in-vitro and in-vivo study is required on these molecules as the binding mode provided hints for the future design of new FAK inhibitors with higher potency and specificity.

Keywords- Veratrum dahuricum, cyclopamine, germine, antitumor activity.

Unique Identification Number - IJEDR1603131
Page Number(s) - 800-805
Pubished in - Volume 4 | Issue 3 | September 2016
DOI (Digital Object Identifier) -   
Publisher - IJEDR (ISSN - 2321-9939)

  Nidhi Tripathi,   "Discovery of inhibitors for focal adhesion kinase (FAK): Molecular modeling study for combating cancer", International Journal of Engineering Development and Research (IJEDR), ISSN:2321-9939, Volume.4, Issue 3, pp.800-805, September 2016, Available at :http://www.ijedr.org/papers/IJEDR1603131.pdf