Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene.
Cycline-dependent kinase 4 (CDK4), an enzyme of the cycline dependent or Ser/Thr protein kinase family, plays a role in cell cycle progression (G1 phase) by phosphorylating a tumor suppressor protein called pRB. Alteration of this enzyme due to missense mutation/ nonsynonymous single nucleotide poly...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0259691 |
| _version_ | 1798034356014415872 |
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| author | Rahatul Islam Mashiur Rahaman Hammadul Hoque Nazmul Hasan Shamsul H Prodhan Asfia Ruhama Nurnabi Azad Jewel |
| author_facet | Rahatul Islam Mashiur Rahaman Hammadul Hoque Nazmul Hasan Shamsul H Prodhan Asfia Ruhama Nurnabi Azad Jewel |
| author_sort | Rahatul Islam |
| collection | DOAJ |
| description | Cycline-dependent kinase 4 (CDK4), an enzyme of the cycline dependent or Ser/Thr protein kinase family, plays a role in cell cycle progression (G1 phase) by phosphorylating a tumor suppressor protein called pRB. Alteration of this enzyme due to missense mutation/ nonsynonymous single nucleotide polymorphisms (nsSNPs) are responsible for various types of cancer progression, e.g. melanoma, lung cancer, and breast cancer. Hence, this study is designed to identify the malignant missense mutation of CDK4 from the single nucleotide polymorphism database (dbSNP) by incorporating computational algorithms. Out of 239 nsSNPs; G15S, D140Y and D140H were predicted to be highly malignant variants which may have a devastating impact on protein structure or function. We also found defective binding motif of these three mutants with the CDK4 inhibitor ribociclib and ATP. However, by incorporating molecular dynamic simulation, our study concludes that the superiority of G15S than the other two mutants (D140Y and D140H) in destabilizing proteins nature. |
| first_indexed | 2024-04-11T20:43:09Z |
| format | Article |
| id | doaj.art-0ed139ea57cc46c6abe020abab650279 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T20:43:09Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0ed139ea57cc46c6abe020abab6502792022-12-22T04:04:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-011611e025969110.1371/journal.pone.0259691Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene.Rahatul IslamMashiur RahamanHammadul HoqueNazmul HasanShamsul H ProdhanAsfia RuhamaNurnabi Azad JewelCycline-dependent kinase 4 (CDK4), an enzyme of the cycline dependent or Ser/Thr protein kinase family, plays a role in cell cycle progression (G1 phase) by phosphorylating a tumor suppressor protein called pRB. Alteration of this enzyme due to missense mutation/ nonsynonymous single nucleotide polymorphisms (nsSNPs) are responsible for various types of cancer progression, e.g. melanoma, lung cancer, and breast cancer. Hence, this study is designed to identify the malignant missense mutation of CDK4 from the single nucleotide polymorphism database (dbSNP) by incorporating computational algorithms. Out of 239 nsSNPs; G15S, D140Y and D140H were predicted to be highly malignant variants which may have a devastating impact on protein structure or function. We also found defective binding motif of these three mutants with the CDK4 inhibitor ribociclib and ATP. However, by incorporating molecular dynamic simulation, our study concludes that the superiority of G15S than the other two mutants (D140Y and D140H) in destabilizing proteins nature.https://doi.org/10.1371/journal.pone.0259691 |
| spellingShingle | Rahatul Islam Mashiur Rahaman Hammadul Hoque Nazmul Hasan Shamsul H Prodhan Asfia Ruhama Nurnabi Azad Jewel Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene. PLoS ONE |
| title | Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene. |
| title_full | Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene. |
| title_fullStr | Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene. |
| title_full_unstemmed | Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene. |
| title_short | Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene. |
| title_sort | computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with cdk4 gene |
| url | https://doi.org/10.1371/journal.pone.0259691 |
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