Molecular docking and dynamic studies of human growth factor receptorbound protein (Grb) 2 insights to identify novel inhibitors
Autor: | J. Rajeswari, Suchitra Mm, Kanipakam Hema, Amineni Umamaheswari, Sandeep S, Pradeep N |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
030103 biophysics biology business.industry Son of Sevenless Computational biology Ligand (biochemistry) Molecular Docking Simulation 03 medical and health sciences Growth factor receptor Docking (molecular) biology.protein Neoplasm Medicine Molecular docking simulation GRB2 biological phenomena cell phenomena and immunity Pharmacophore business GRB2 adapter protein Proto-oncogene tyrosine-protein kinase Src |
Zdroj: | Journal of Clinical and Scientific Research, Vol 5, Iss 4, Pp 252-258 (2016) |
ISSN: | 2277-8357 2277-5706 |
Popis: | Background: Human growth factor receptor bound protein-2 (Grb 2) involves in initiation of kinase signaling by Son of Sevenless (SOS) and activates mitogen activated protein kinase pathway. Grb2 overexpress during cancerous condition hence it emerged as a potent target for various cancers. Material and Methods: Seven pharmacophores were developed from seven co-crystal structures of Grb2 and applied for common pharmacophore hypothesis. Two common pharmacophore hypothesis (CPH) models were screened and hits were applied for docking and free energy [ΔG] calculations. Results: Two leads were proposed from docking and ΔG analysis. Energy of the system, RMSD, RMSF, hydrogen bonds and water bridges of lead1 was better than the co-crystal ligand during 50 ns molecular dynamics simulations. Discussion: Two leads are interacting with Src homology 2 (SH2) domain of Grb2 and blocking the function of Grb2. |
Databáze: | OpenAIRE |
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