Probing the structural impacts of arg388 replacements in pkp2 protein complex: spesific case in arvc

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2022-10

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Kutlu, Aslı
Şahin, Şuara
Özkan, Mehmet Emre
Ulukaya, Engin

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In this study, we aimed to probe the roles of missense variants in PKP2 protein structures in ARVC-related clinics. Within the structure of PKP2 protein, there were many missense var-iants, whose associations with ARVC were partially reported mostly with a genetic screening approach. Especially in the position of Arg388 in PKP2 protein, 4 missense variants (Trp, Pro, Gly, and Gln) were reported but onlythe associations of Arg388Trp and Arg388Prowith ARVCwere reported as ‘pathogenic’ and others were VUS. To predict the impacts of the remaining two missense variants (Arg388Gln/Gly) in PKP2, we performed 100 ns classical all-atom molecular dy-namics simulations and then compared the structural features of native and mutant protein structures to speculate more about the categorization of Arg388Gln and Arg388Gly vari-ants as pathogenic or not. The changes in intramolecular in-teractions with RMSD and Rg patterns ofnative and mutant protein structures have suggested that the structural altera-tions caused by the presence of Arg388Trp and Arg388Pro were so similar to those of caused by Arg388Gly and Arg388Gln. These structural changes were also confirmed by the correlation coefficient calculations performed based on RMSD patterns of native and mutant protein structures. Here,the main principle in protein science about similar structure associations withsimilar functions was applied into the pre-dictions of VUS missense variants in Arg388 of PKP2 protein structure by gained the structural insights gained by cMD simulations. Based on our cMD results, Arg388Gly and Arg388Gln also seem to be ‘pathogenic’ by sharing similar structural features withArg388Trp and Arg388Pro.

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https://hibit2022.ims.metu.edu.tr/
https://hdl.handle.net/11511/101311

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The International Symposium on Health Informatics and Bioinformatics

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Graduate School of Informatics, Conference / Seminar

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Citation Formats

A. Kutlu, Ş. Şahin, M. E. Özkan, and E. Ulukaya, “Probing the structural impacts of arg388 replacements in pkp2 protein complex: spesific case in arvc,” Erdemli, Mersin, TÜRKİYE, 2022, p. 1053, Accessed: 00, 2023. [Online]. Available: https://hibit2022.ims.metu.edu.tr/.