Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s Disease (AD)
The association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s disease (AD) remains unclear. The major aim of this study was to elucidate the role of genes and molecular targets in <i>P. gingivalis</i>-associated AD. Two Gene Expres...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5432 |
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| author | Ahmed Hamarsha Kumarendran Balachandran Ahmad Tarmidi Sailan Nurrul Shaqinah Nasruddin |
| author_facet | Ahmed Hamarsha Kumarendran Balachandran Ahmad Tarmidi Sailan Nurrul Shaqinah Nasruddin |
| author_sort | Ahmed Hamarsha |
| collection | DOAJ |
| description | The association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s disease (AD) remains unclear. The major aim of this study was to elucidate the role of genes and molecular targets in <i>P. gingivalis</i>-associated AD. Two Gene Expression Omnibus (GEO) datasets, GSE5281 for AD (n = 84 Alzheimer’s, n = 74 control) and GSE9723 (n = 4 <i>P. gingivalis</i>, n = 4 control), were downloaded from the GEO database. Differentially expressed genes (DEGs) were obtained, and genes common to both diseases were drawn. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis was performed from the top 100 genes (50 upregulated and 50 downregulated genes). We then proceeded with CMap analysis to screen for possible small drug molecules targeting these genes. Subsequently, we performed molecular dynamics simulations. A total of 10 common genes (CALD1, HES1, ID3, PLK2, PPP2R2D, RASGRF1, SUN1, VPS33B, WTH3DI/RAB6A, and ZFP36L1) were identified with a <i>p</i>-value < 0.05. The PPI network of the top 100 genes showed UCHL1, SST, CHGB, CALY, and INA to be common in the MCC, DMNC, and MNC domains. Out of the 10 common genes identified, only 1 was mapped in CMap. We found three candidate small drug molecules to be a fit for PLK2, namely PubChem ID: 24971422, 11364421, and 49792852. We then performed molecular docking of PLK2 with PubChem ID: 24971422, 11364421, and 49792852. The best target, 11364421, was used to conduct the molecular dynamics simulations. The results of this study unravel novel genes to <i>P. gingivalis</i>-associated AD that warrant further validation. |
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| language | English |
| last_indexed | 2024-03-11T06:26:38Z |
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| spelling | doaj.art-f621c5f22c414ed5b918fe99a7f5a2412023-11-17T11:33:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246543210.3390/ijms24065432Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s Disease (AD)Ahmed Hamarsha0Kumarendran Balachandran1Ahmad Tarmidi Sailan2Nurrul Shaqinah Nasruddin3Department of Craniofacial Diagnostics and Biosciences, Faculty of Dentistry, University Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, MalaysiaDepartment of Craniofacial Diagnostics and Biosciences, Faculty of Dentistry, University Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, MalaysiaDepartment of Craniofacial Diagnostics and Biosciences, Faculty of Dentistry, University Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, MalaysiaDepartment of Craniofacial Diagnostics and Biosciences, Faculty of Dentistry, University Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, MalaysiaThe association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s disease (AD) remains unclear. The major aim of this study was to elucidate the role of genes and molecular targets in <i>P. gingivalis</i>-associated AD. Two Gene Expression Omnibus (GEO) datasets, GSE5281 for AD (n = 84 Alzheimer’s, n = 74 control) and GSE9723 (n = 4 <i>P. gingivalis</i>, n = 4 control), were downloaded from the GEO database. Differentially expressed genes (DEGs) were obtained, and genes common to both diseases were drawn. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis was performed from the top 100 genes (50 upregulated and 50 downregulated genes). We then proceeded with CMap analysis to screen for possible small drug molecules targeting these genes. Subsequently, we performed molecular dynamics simulations. A total of 10 common genes (CALD1, HES1, ID3, PLK2, PPP2R2D, RASGRF1, SUN1, VPS33B, WTH3DI/RAB6A, and ZFP36L1) were identified with a <i>p</i>-value < 0.05. The PPI network of the top 100 genes showed UCHL1, SST, CHGB, CALY, and INA to be common in the MCC, DMNC, and MNC domains. Out of the 10 common genes identified, only 1 was mapped in CMap. We found three candidate small drug molecules to be a fit for PLK2, namely PubChem ID: 24971422, 11364421, and 49792852. We then performed molecular docking of PLK2 with PubChem ID: 24971422, 11364421, and 49792852. The best target, 11364421, was used to conduct the molecular dynamics simulations. The results of this study unravel novel genes to <i>P. gingivalis</i>-associated AD that warrant further validation.https://www.mdpi.com/1422-0067/24/6/5432Alzheimer’s disease<i>Porphyromonas gingivalis</i>bioinformatics |
| spellingShingle | Ahmed Hamarsha Kumarendran Balachandran Ahmad Tarmidi Sailan Nurrul Shaqinah Nasruddin Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s Disease (AD) International Journal of Molecular Sciences Alzheimer’s disease <i>Porphyromonas gingivalis</i> bioinformatics |
| title | Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s Disease (AD) |
| title_full | Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s Disease (AD) |
| title_fullStr | Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s Disease (AD) |
| title_full_unstemmed | Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s Disease (AD) |
| title_short | Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) and Alzheimer’s Disease (AD) |
| title_sort | predicting key genes and therapeutic molecular modelling to explain the association between i porphyromonas gingivalis i i p gingivalis i and alzheimer s disease ad |
| topic | Alzheimer’s disease <i>Porphyromonas gingivalis</i> bioinformatics |
| url | https://www.mdpi.com/1422-0067/24/6/5432 |
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