STRUCTURAL AND DYNAMIC PROPERTIES OF MUTANTS OF THE SOD1 PROTEIN ASSOCIATED WITH AMYOTROPHIC LATERAL SCLEROSIS
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which affects motor neurons in the brain and spinal cord and leads to patients’ death. One of the causes of motor neuron degeneration and death is the formation of intracellular protein aggregates formed by a mutant SOD1 protein. Re...
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| Format: | Article |
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2015-01-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/322 |
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| _version_ | 1832575326123720704 |
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| author | N. A. Alemasov N. V. Ivanisenko V. A. Ivanisenko |
| author_facet | N. A. Alemasov N. V. Ivanisenko V. A. Ivanisenko |
| author_sort | N. A. Alemasov |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which affects motor neurons in the brain and spinal cord and leads to patients’ death. One of the causes of motor neuron degeneration and death is the formation of intracellular protein aggregates formed by a mutant SOD1 protein. Recently, it has been shown that the survival time of ALS patients with specific mutation in SOD1 gene inversely correlates with thermodynamic stability of the SOD1 mutant protein. In the present paper, we hypothesize that mutant SOD1 aggregation can be facilitated by not only destabilization due to hydrogen bonds disruption but also by formation of new hydrogen bonds, which can stabilize intermediate “pathogenic” conformations of the mutant SOD1 protein. Molecular dynamics simulations were conducted to estimate frequencies of hydrogen bond occurrence in the protein structure. It was shown that the regression model based on frequencies of hydrogen bond occurrence significantly better correlated with patients’ survival time (R = 0.89, p < 0.00001) than the estimation based on thermodynamic stability analysis of mutant SOD1 proteins. |
| format | Article |
| id | doaj-art-bce3c7f28cb549758bfe783f2b2042bb |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-bce3c7f28cb549758bfe783f2b2042bb2025-02-01T09:58:01ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592015-01-01184/2920927305STRUCTURAL AND DYNAMIC PROPERTIES OF MUTANTS OF THE SOD1 PROTEIN ASSOCIATED WITH AMYOTROPHIC LATERAL SCLEROSISN. A. Alemasov0N. V. Ivanisenko1V. A. Ivanisenko2Institute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which affects motor neurons in the brain and spinal cord and leads to patients’ death. One of the causes of motor neuron degeneration and death is the formation of intracellular protein aggregates formed by a mutant SOD1 protein. Recently, it has been shown that the survival time of ALS patients with specific mutation in SOD1 gene inversely correlates with thermodynamic stability of the SOD1 mutant protein. In the present paper, we hypothesize that mutant SOD1 aggregation can be facilitated by not only destabilization due to hydrogen bonds disruption but also by formation of new hydrogen bonds, which can stabilize intermediate “pathogenic” conformations of the mutant SOD1 protein. Molecular dynamics simulations were conducted to estimate frequencies of hydrogen bond occurrence in the protein structure. It was shown that the regression model based on frequencies of hydrogen bond occurrence significantly better correlated with patients’ survival time (R = 0.89, p < 0.00001) than the estimation based on thermodynamic stability analysis of mutant SOD1 proteins.https://vavilov.elpub.ru/jour/article/view/322sod1neurodegenerative diseasesmolecular dynamicshydrogen bondspredictionsurvival time |
| spellingShingle | N. A. Alemasov N. V. Ivanisenko V. A. Ivanisenko STRUCTURAL AND DYNAMIC PROPERTIES OF MUTANTS OF THE SOD1 PROTEIN ASSOCIATED WITH AMYOTROPHIC LATERAL SCLEROSIS Вавиловский журнал генетики и селекции sod1 neurodegenerative diseases molecular dynamics hydrogen bonds prediction survival time |
| title | STRUCTURAL AND DYNAMIC PROPERTIES OF MUTANTS OF THE SOD1 PROTEIN ASSOCIATED WITH AMYOTROPHIC LATERAL SCLEROSIS |
| title_full | STRUCTURAL AND DYNAMIC PROPERTIES OF MUTANTS OF THE SOD1 PROTEIN ASSOCIATED WITH AMYOTROPHIC LATERAL SCLEROSIS |
| title_fullStr | STRUCTURAL AND DYNAMIC PROPERTIES OF MUTANTS OF THE SOD1 PROTEIN ASSOCIATED WITH AMYOTROPHIC LATERAL SCLEROSIS |
| title_full_unstemmed | STRUCTURAL AND DYNAMIC PROPERTIES OF MUTANTS OF THE SOD1 PROTEIN ASSOCIATED WITH AMYOTROPHIC LATERAL SCLEROSIS |
| title_short | STRUCTURAL AND DYNAMIC PROPERTIES OF MUTANTS OF THE SOD1 PROTEIN ASSOCIATED WITH AMYOTROPHIC LATERAL SCLEROSIS |
| title_sort | structural and dynamic properties of mutants of the sod1 protein associated with amyotrophic lateral sclerosis |
| topic | sod1 neurodegenerative diseases molecular dynamics hydrogen bonds prediction survival time |
| url | https://vavilov.elpub.ru/jour/article/view/322 |
| work_keys_str_mv | AT naalemasov structuralanddynamicpropertiesofmutantsofthesod1proteinassociatedwithamyotrophiclateralsclerosis AT nvivanisenko structuralanddynamicpropertiesofmutantsofthesod1proteinassociatedwithamyotrophiclateralsclerosis AT vaivanisenko structuralanddynamicpropertiesofmutantsofthesod1proteinassociatedwithamyotrophiclateralsclerosis |