{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:33:33Z","timestamp":1787027613562,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T00:00:00Z","timestamp":1629504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018R1C1B600814"],"award-info":[{"award-number":["NRF-2018R1C1B600814"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1C1B3007144"],"award-info":[{"award-number":["NRF-2017R1C1B3007144"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Melanoma differentiation-associated protein 5 (MDA5) is a crucial RIG-I-like receptor RNA helicase enzyme encoded by IFIH1 in humans. Single nucleotide polymorphisms in the IFIH1 results in fatal genetic disorders such as Aicardi\u2013Gouti\u00e8res syndrome and Singleton\u2013Merten syndrome, and in increased risk of type I diabetes in humans. In this study, we chose four different amino acid substitutions of the MDA5 protein responsible for genetic disorders: MDA5L372F, MDA5A452T, MDA5R779H, and MDA5R822Q and analyzed their structural and functional relationships using molecular dynamic simulations. Our results suggest that the mutated complexes are relatively more stable than the wild-type MDA5. The radius of gyration, interaction energies, and intra-hydrogen bond analysis indicated the stability of mutated complexes over the wild type, especially MDA5L372F and MDA5R822Q. The dominant motions exhibited by the wild-type and mutant complexes varied significantly. Moreover, the betweenness centrality of the wild-type and mutant complexes showed shared residues for intra-signal propagation. The observed results indicate that the mutations lead to a gain of function, as reported in previous studies, due to increased interaction energies and stability between RNA and MDA5 in mutated complexes. These findings are expected to deepen our understanding of MDA5 variants and may assist in the development of relevant therapeutics against the disorders.<\/jats:p>","DOI":"10.3390\/biom11081251","type":"journal-article","created":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T21:42:12Z","timestamp":1629668532000},"page":"1251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Computational Insights into the Structural Dynamics of MDA5 Variants Associated with Aicardi\u2013Gouti\u00e8res Syndrome and Singleton\u2013Merten Syndrome"],"prefix":"10.3390","volume":"11","author":[{"given":"Vijayakumar","family":"Gosu","sequence":"first","affiliation":[{"name":"Department of Animal Biotechnology, Jeonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0204-0263","authenticated-orcid":false,"given":"Santanu","family":"Sasidharan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, National Institute of Technology, Warangal 506004, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Saudagar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, National Institute of Technology, Warangal 506004, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hak-Kyo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Animal Biotechnology, Jeonbuk National University, Jeonju 54896, Korea"},{"name":"Department of Agricultural Convergence Technology, Jeonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0819-0553","authenticated-orcid":false,"given":"Donghyun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Agricultural Convergence Technology, Jeonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-immunol-032414-112240","article-title":"Innate immune pattern recognition: A cell biological perspective","volume":"33","author":"Brubaker","year":"2015","journal-title":"Annu. 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