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Investigation of Molecular Interactions of VEGFR and its Inhibitors by Molecular Dynamics Simulation

Didandeh, Mohsen | 2020

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 53588 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Bastani, Daruoosh; Mashayekhan, Shohreh; Karami, Layla
  7. Abstract:
  8. One of the chief kinds of receptors in cancer angiogenesis is the tyrosine kinase VEGFR-2. This target receptor is presented in both forms; active and inactive. adenosine triphosphate (ATP) residue is the location of deformational change from inactive to active form. Small molecule inhibitors have been designed for various forms of this receptor. In current study, the interaction of small molecular inhibitors including; Regorafenib, Cabozantinib and Thiosanib with dual VEGFR-2 receptor forms was investigated by molecular dynamics with Gromacs software. Cabozantinib and Regorafenib inhibitors had a lower binding energy in interaction with the inactive state however, Thiosanib inhibitors in interaction with the active state of VEGFR-2, which means a more appropriate interaction. Also, the binding energies obtained from the simulation have a good correlation with the IC50s obtained from previous experimental studies (R2 = 0.999). The most effective amino acids in this simulation were obtained by MM-PBSA method, which are: C1045, L1035, L889, V916, V848 and L840. The mentioned results are in good agreement with previous researches. The recent computational results can be used in future research to design more effective drugs
  9. Keywords:
  10. Molecular Dynamic Simulation ; Inhibitor ; Angiogenesis ; Tumors ; Vascular Endothelial Growth Factor (VEGF)

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