The future of HOPE: what can and cannot be predicted about the molecular effects of a disease causing point mutation in a protein?

Camilli, Francesca; Borrmann, Annika; Gholizadeh, Shima; Beek, Tim Ah te; Kuipers, Remko; Venselaar, Hanka

doi:10.14806/ej.17.1.212

Cited by 3 publications

(1 citation statement)

References 33 publications

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“…PolyPhen is a computational tool for identification of potentially functional nsSNPs. We took the SNPs in binding domains predicted by both databases SIFT and PolyPhen to be deleterious and damaging (3 SNPs; rs145061115, rs199824195 and rs201797884) to Predict the molecular phenotypic effects of these SNPs using Project HOPE ( http://www.cmbi.ru.nl/hope/) (22). It is an online web-server used to search protein 3D structures with explanation of such a change in both structure and function of the protein, we entered the three SNPs (rs145061115, rs199824195, and rs201797884) that we obtained from the last step with the primary structure of the CCR5 protein (obtained from uniport) into HOPE.…”

Section: Methodsmentioning

confidence: 99%

In silico analysis of single nucleotide polymorphisms (SNPs) in human C-C chemokine receptor type five (CCR5) gene

Aah

Ibrahim

2020

Preprint

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IntroductionChemokines are small transmembrane proteins with immune surveillance and immune cell recruitment functions. the expression of CCR5 gene affects virus production and viral load(1). The CCR5 gene contains two introns, three exons, and two promoters, and it is necessary as a co-receptor for the entry of the macrophage-tropic HIV strains. Mutations in the coding region of CCR5 affect the protein structure, which will affect production, chemokine binding, transport, signaling and expression of the CCR5 receptor.MethodsSNPs within CCR5 gene were retrieved from ensemble database. Coding SNPs were analyzed using SNPnexus. Coding non-synonymous SNPs in CCR5 binding domains with Viral gp120 were analyzed using SIFT, PolyPhen and I-mutant tools. Project HOPE then used to modelled the 3D structure of the protein resulting from these SNPs. Non-coding SNPs that affects miRNAs in 3’ rejoin were analyzing using PolymiRTS. SNPs that affect transcription factor binding were analyzed using regulomeDB.Results(178) non-synonyms missense SNPs were found to have deleterious and damaging effect on the structure and function of the protein. In CCR5 binding domains with Viral gp120: 3 SNPs rs145061115, rs199824195 and rs201797884 were found to affect both structure and function and stability of chemokine protein. The 2 SNPs rs185691679 and rs199722070 has a role in disruption and creation of the target sites in miRNA seeds due to their high conservation score.ConclusionMutations in CCR5 gene may explain and represent the molecular basis of the resistance to HIV infection.

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Section: Methodsmentioning

confidence: 99%

In silico analysis of single nucleotide polymorphisms (SNPs) in human C-C chemokine receptor type five (CCR5) gene

Aah

Ibrahim

2020

Preprint

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The targeted next-generation sequence revealed SMAD4, AKT1, and TP53 mutations from circulating cell-free DNA of breast cancer and its effect on protein structure – A computational approach

Balasundaram

et al. 2023

Journal of Biomolecular Structure and Dynamics

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Exon globin mutation of β-thalassemia in Indonesian ethnic groups: A bioinformatics approach

2017

Advances in Biomolecular Medicine

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The future of HOPE: what can and cannot be predicted about the molecular effects of a disease causing point mutation in a protein?

Cited by 3 publications

References 33 publications

In silico analysis of single nucleotide polymorphisms (SNPs) in human C-C chemokine receptor type five (CCR5) gene

In silico analysis of single nucleotide polymorphisms (SNPs) in human C-C chemokine receptor type five (CCR5) gene

The targeted next-generation sequence revealed SMAD4, AKT1, and TP53 mutations from circulating cell-free DNA of breast cancer and its effect on protein structure – A computational approach

Exon globin mutation of β-thalassemia in Indonesian ethnic groups: A bioinformatics approach

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