Molecular docking and dynamic studies of human growth factor receptorbound protein (Grb) 2 insights to identify novel inhibitors

Abstract

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 [G] calculations. Results: Two leads were proposed from docking and G 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.

Keywords

• Neoplasm
• GRB2 adapter protein
• Molecular docking simulation