Next-generation version of recombinant human interferon-beta: A molecular dynamic simulation study
The ability of recombinant human interferon beta-1b (IFNβ-1b) to elicit the production of anti-IFNβ-1b antibodies becomes a significant issue for interferon therapy in patients. Mitigating the immunogenicity issues requires understanding the stimulating factors in observed immune responses. Among mu...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Informatics in Medicine Unlocked |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352914822001782 |
| _version_ | 1798003165773168640 |
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| author | Mohadeseh Haji Abdolvahab Rayeheh Vafaee S. Shahriar Arab Mehrdad Behmanesh |
| author_facet | Mohadeseh Haji Abdolvahab Rayeheh Vafaee S. Shahriar Arab Mehrdad Behmanesh |
| author_sort | Mohadeseh Haji Abdolvahab |
| collection | DOAJ |
| description | The ability of recombinant human interferon beta-1b (IFNβ-1b) to elicit the production of anti-IFNβ-1b antibodies becomes a significant issue for interferon therapy in patients. Mitigating the immunogenicity issues requires understanding the stimulating factors in observed immune responses. Among multiple factors, epitopes might be the main reason for the observed immunogenicity of this drug. In this study, we investigate the ability of epitopes in IFNβ-1b to bind to the MHC class II receptors. We applied point mutations to reduce the binding affinity of the existing epitopes of IFNβ-1b to MHC class II molecules. Several bioinformatics methods were applied to compare the binding affinity of both native and mutated epitopes to the MHC class II receptors. We identified three residues, Tyrosine 3, Tyrosine 132, and Glycine 162, that if altered to Leucine, Leucine, and Glutamate, respectively, leads to a decline in the binding affinity of IFNβ-1 b's epitope to the MHC class II receptors.This suggests that we can decline the binding affinity of therapeutic IFNβ-1b in silico by introducing those point mutations. |
| first_indexed | 2024-04-11T12:03:35Z |
| format | Article |
| id | doaj.art-f9ec7820bd6c49b1bbd7e0c9b5ba0e8d |
| institution | Directory Open Access Journal |
| issn | 2352-9148 |
| language | English |
| last_indexed | 2024-04-11T12:03:35Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Informatics in Medicine Unlocked |
| spelling | doaj.art-f9ec7820bd6c49b1bbd7e0c9b5ba0e8d2022-12-22T04:24:47ZengElsevierInformatics in Medicine Unlocked2352-91482022-01-0132101036Next-generation version of recombinant human interferon-beta: A molecular dynamic simulation studyMohadeseh Haji Abdolvahab0Rayeheh Vafaee1S. Shahriar Arab2Mehrdad Behmanesh3Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, 1517964311, Iran; Department of Genetics, Tarbiat Modares University, Tehran, IranDepartment of Biophysics, Tarbiat Modarres University, Tehran, IranDepartment of Biophysics, Tarbiat Modarres University, Tehran, Iran; Corresponding author. Jalal Ale Ahmad, Nasr, Tehran, P.O.Box: 14115-111, Iran.Department of Genetics, Tarbiat Modares University, Tehran, Iran; Corresponding author.The ability of recombinant human interferon beta-1b (IFNβ-1b) to elicit the production of anti-IFNβ-1b antibodies becomes a significant issue for interferon therapy in patients. Mitigating the immunogenicity issues requires understanding the stimulating factors in observed immune responses. Among multiple factors, epitopes might be the main reason for the observed immunogenicity of this drug. In this study, we investigate the ability of epitopes in IFNβ-1b to bind to the MHC class II receptors. We applied point mutations to reduce the binding affinity of the existing epitopes of IFNβ-1b to MHC class II molecules. Several bioinformatics methods were applied to compare the binding affinity of both native and mutated epitopes to the MHC class II receptors. We identified three residues, Tyrosine 3, Tyrosine 132, and Glycine 162, that if altered to Leucine, Leucine, and Glutamate, respectively, leads to a decline in the binding affinity of IFNβ-1 b's epitope to the MHC class II receptors.This suggests that we can decline the binding affinity of therapeutic IFNβ-1b in silico by introducing those point mutations.http://www.sciencedirect.com/science/article/pii/S2352914822001782Interferon-betaEpitopeVariant proteinImmunogenicityMHC class II |
| spellingShingle | Mohadeseh Haji Abdolvahab Rayeheh Vafaee S. Shahriar Arab Mehrdad Behmanesh Next-generation version of recombinant human interferon-beta: A molecular dynamic simulation study Informatics in Medicine Unlocked Interferon-beta Epitope Variant protein Immunogenicity MHC class II |
| title | Next-generation version of recombinant human interferon-beta: A molecular dynamic simulation study |
| title_full | Next-generation version of recombinant human interferon-beta: A molecular dynamic simulation study |
| title_fullStr | Next-generation version of recombinant human interferon-beta: A molecular dynamic simulation study |
| title_full_unstemmed | Next-generation version of recombinant human interferon-beta: A molecular dynamic simulation study |
| title_short | Next-generation version of recombinant human interferon-beta: A molecular dynamic simulation study |
| title_sort | next generation version of recombinant human interferon beta a molecular dynamic simulation study |
| topic | Interferon-beta Epitope Variant protein Immunogenicity MHC class II |
| url | http://www.sciencedirect.com/science/article/pii/S2352914822001782 |
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