| Journal: | Brazilian Journal of Pharmaceutical Sciences |
| Database: | PERIÓDICA |
| System number: | 000451692 |
| ISSN: | 1984-8250 |
| Authors: | Barkhordari, Farzaneh1 Rismani, Elham2 Tabasinezhad, Maryam1 Asgari, Saeme1 Nematollahi, Leila1 Talebkhan, Yeganeh1 |
| Institutions: | 1Pasteur Institute of Iran, Biotechnology Research Center, Teherán. Irán 2Pasteur Institute of Iran, Molecular Medicine Department, Teherán. Irán |
| Year: | 2022 |
| Volumen: | 58 |
| Country: | Brasil |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Experimental, aplicado |
| English abstract | The present study deals with the computational design and analysis of a novel fusion protein based on a single chain variable fragment that binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2) in breast cancer cells. Alpha luffin, a small ribosome inactivating protein (RIP), was attached to the anti-HER2 antibody fragment. I-TASSER modeling provided the full-length structure of the fusion protein. Molecular docking evaluated the molecular interactions of the complementarity-determining regions of designed fusion protein to HER2. Energy minimization and molecular dynamics simulations were conducted to refine the complexes. RMSD plot revealed reasonable stability of the fusion protein during the simulation. The free binding energy profile of complexes affirmed a favorable binding affinity of proteins in complex with HER2 using molecular mechanics Poisson-Boltzmann surface area (G-MMPBSA) algorithm. In general, this approach looks promising in the development of new fusion proteins in terms of immunotoxins with appropriate cytotoxicity |
| Disciplines: | Química |
| Keyword: | Química farmacéutica, Cáncer, Terapia dirigida, Proteínas de fusión, Dinámica molecular, Inmunotoxinas |
| Keyword: | Medicinal chemistry, Cancer, Targeted therapy, Fusion proteins, Molecular dynamics, Immunotoxins |
| Full text: | Texto completo (Ver HTML) Texto completo (Ver PDF) |
