Computational Insights into the Structural Dynamics of MDA5 Variants Associated with Aicardi-Goutieres Syndrome and Singleton-Merten Syndrome.

ABSTRACT: 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-Goutières syndrome and Singleton-Merten 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: MDA5^L372F, MDA5^A452T, MDA5^R779H, and MDA5^R822Q 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

SUBMITTER: Gosu V 

PROVIDER: S-EPMC8393256 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature