Samira Talebi, Alireza Saeedinia*, Mehdi Zeinoddini, Fathollah Ahmadpour and Majid Sadeghizadeh Pages 71 - 76 ( 6 )
Background: Human IFN-α is a family of structurally related proteins that exhibit a wide range of antiproliferative and antiviral activities. IFNs bind to a specific cell receptor as the IFN-α/β receptor (IFNAR) that compose of IFNAR1 and IFNAR2 chains. Interferon’s affinity for IFNAR1 and IFNAR2 chains changes the type of its activity.
Objective: To understand the structural basis for these different activities, some important amino acid residues in this study binding region of interferon to IFNAR1 were replaced to more effective ones.
Method: In order to suggestion of the important amino acids for mutation, the imperative area IFN- α were distinguished based on previous reports and structural properties including Vander Waals energy, electrostatic energy, length of the hydrogen bands and other biological property of selected and substituted amino acids. Both the IFN-α2b and its receptor IFNAR1 have been modeled followed by Easy Modeler2 software and all of the structures were confirmed by server MDWEB and VMD software. Then, the interaction studies between two protein have been done using protein-protein docking (HADDOCK 2.2) for both native and mutant forms.
Results: HADDOCK results for investigation of IFN-α2b and IFNAR1 interactions in both native and mutant forms shown that binding of mutant forms to IFNAR1 have been enhanced.
Conclusion: In silico study of IFN mutants have provided a powerful tool for studying the structure and function of these molecules. Moreover, these engineered IFNs may have important new therapeutic applications and may provide more sights into understanding of the clinical activities of these molecules.
Binding, IFNAR1, In Silico study, interferon, mutations, protein structure.
Department of Biosciences and Biotechnology, Malek Ashtar University of Technology, Tehran, Department of Biosciences and Biotechnology, Malek Ashtar University of Technology, Tehran, Department of Biosciences and Biotechnology, Malek Ashtar University of Technology, Tehran, Applied Biotechnology Research Centre, Baqiyatallah University of Medical Sciences, Tehran, Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran