In silico designing and optimization of anti-breast cancer antibody mimetic oligopeptide targeting HER-2 in women.
Overexpression of HER-2 is of frequent (20-30%) occurrence in breast cancer. Therapeutic targeting of HER-2 with humanized antibody derived oligopeptide may be a promising approach to the treatment of breast cancer. HER-2 gene is part of a family of genes that play critical roles in regulating transmembrane growth of breast cancer cells. Pertuzumab, a recombinant humanized monoclonal antibody (2C4), binds to extracellular domain II of the HER-2 receptor and inhibits its ability to dimerize with other HER receptors blocking the cell growth, signaling and apoptosis induction. The unique binding pocket on HER-2 for pertuzumab provides an important target domain for creation of new anticancer drugs. In the present work an efficient oligopeptide was designed by our computational method that interacts with pertuzumab binding sites of HER-2. In silico docking study demonstrated the best specific interaction of RASPADREV oligopeptide with the dimerization domain in the HER-2 molecule among various screened oligopeptides. ADMET and SAR properties prove the drug likeness of designed oligopeptide as having value 0.98.
Akhoon
Bashir A
BA
Centre of Bioinformatics, Department of Biotechnology, SMVD University, Jammu, India. bashirakhlaq@gmail.com
Gupta
Shishir K
SK
Verma
Vijeshwar
V
Dhaliwal
Gagan
G
Srivastava
Mugdha
M
Gupta
Shailendra K
SK
Ahmad
Raja Feroz
RF
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000737:chemistry*; D001943:Breast Neoplasms / Q000276:immunology*; D019295:Computational Biology / Q000379:methods*; D015195:Drug Design; D005260:Female; D006801:Humans; D007526:Isoelectric Point; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000276:immunology*; D013816:Thermodynamics
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D009842:Oligopeptides; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C485206:pertuzumab