Affinity enhancement of HER2-binding Z(HER2:342) affibody via rational design approach: a molecular dynamics study |
| |
| Authors: | Mohammad Ali Ghaffari Majid Zeinali Ebrahim Barzegari Asadabadi |
| |
| Affiliation: | 1. Department of Biochemistry, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.;2. Biotechnology Research Center, Research Institute of Petroleum Industry, Tehran, Iran.;3. Faculty of Biological Sciences, Department of Biophysics, Tarbiat Modares University, Tehran, Iran. |
| |
| Abstract: | Human epidermal growth factor receptor 2 (HER2) contributes to the development of breast cancers and malignancies. On the other hand, engineered affibody Z(HER2:342) that binds to HER2 can be successfully used for both diagnostic purposes and specific ablation of malignant HER2-positive cell lines. In the current study, electrostatics-based prediction was applied for improving Z(HER2:342) binding affinity using computational design. The affibody Z(HER2:342) alone and in complex with HER2 was energetically minimized, solvated in explicit water, and neutralized. After heating and equilibration steps, the system was studied by isothermal-isobaric (NPT) MD simulation. According to trajectories, Z(HER2:342) specifically binds to HER2 through hydrogen bonds and salt bridges. Based on the electrostatic binding contributions, two affinity-matured variants namely V1 (Tyr35Arg) and V2 (Asn6Asp and Met9Glu) were rationally designed. More investigations through MD simulation show that V1 interacts with HER2 receptor more strongly, compared to Z(HER2:342) and V2. |
| |
| Keywords: | Z(HER2:342) affibody EGFRs affinity enhancement molecular dynamics simulation |
|
|
