Abstract
Purpose: Interferon beta (IFN-β) is used to combat multiple sclerosis (MS) disease. Creating R27T and V101F mutations (mHuIFN-β-27 and mHuIFN-β-101) is one of the tasks performed to improve human interferon beta (HuIFN-β) half-life, function and expression. In this work, the impact of R27T and V101F mutations in recombinant IFN-β on its binding to interferon receptors were studied by molecular docking. Methods: This work was performed through in silico study. The simulation of mutation was performed using the online Rosetta Backrub software and checked using server verify3D. Comparison of access to the solvent of the amino acids in the structures created was performed using the asaview online server. Also, the effect of mutations on the fold of the protein was reviewed by the online HOPE server. The molecular docking was performed between HuIFN-β and the external region of IFNAR receptor using the online ClusPro2 protein-protein docking server. Results: The comparison of the values of the negative binding energy (ΔGbind) obtained from protein-protein molecular docking between IFNAR receptor and HuIFN-β, mHuIFN-β-27, mHuIFN-β-101 and mHuIFN-β-27-101 ligands did not show a significant difference, and these differences do not see any meaningful relationship between them (P > 0.9999). Conclusion: Regarding these results, it can be concluded that these mutations do not have a negative effect on the composition of the complex rHuIFN-β/IFNAR. So, they do not interfere with the binding of the IFN-β to the receptor. It is concluded that the quality of the rHuIFN-β is improved by introducing these two mutations.
Highlights
Multiple sclerosis (MS) is a chronic disorder of the central nervous system, which, as a result of autoimmune attacks on the neural tissue, classically damages the macular degeneration of the axon and leads to the formation of polygonal lesions in the white matter.[1,2,3] MS is phenotypically divided into several groups, the most common of which is the relapsing-remitting multiple sclerosis (RRMS).[3]
The mHuIFN-β-27, mHuIFN-β-101 and mHuIFN-β-27-101 structures were simulated on the basis of the crystalline structure HuIFN-β (PDB ID: 1AU1) in the Rosetta Bakrub server, and the structures with the highest score were selected
It can be said that the creation of the mutations R27T and V101F in HuIFN-β, despite the presence of these
Summary
Multiple sclerosis (MS) is a chronic disorder of the central nervous system, which, as a result of autoimmune attacks on the neural tissue, classically damages the macular degeneration of the axon and leads to the formation of polygonal lesions in the white matter.[1,2,3] MS is phenotypically divided into several groups, the most common of which is the relapsing-remitting multiple sclerosis (RRMS).[3]. Interferons were discovered for the first time due to their antiviral properties in 1957 by Isaacs and Lindenmann.[4] Today, a wide range of functions is evident in diverse biological fields such as defense against microbial infections, antiviral, anticancer, autoimmune, inflammatory, immunization, proliferation, differentiation and survival of the cell.[4,5,6] These small messenger molecules (kDa 30>) are secreted by various cells of the vertebrates in response to various stimuli that play an important role in maintaining health.[1,5,7] Interferons were the first cytokines that were used for therapeutic purposes as natural forms or recombinant forms in humans.[8] In recent years, the therapeutic effects of various interferons have been identified on the treatment of various diseases, including hepatitis, cancers, autoimmune diseases, MS, and their importance in well-established therapeutic programs.[9,10,11] The expression of type I and type III interferons usually increase significantly during viral infections, which indicates their role in controlling viral infections.[4] In human, type I contains human interferon alpha (HuIFN-α; which has more than 12 encoding genes), HuIFN-β, HuIFN-ω, HuIFN-ε, and HuIFN-κ, which range in length from 172-165 amino acids. Type I interferons are known for their function in the immune system, but play a
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