| Title |
Methylation-targeted specificity of the DNA binding proteins R.DpnI and MeCP2 studied by molecular dynamics simulations
|
|---|---|
| Published in |
Journal of Molecular Modeling, April 2017
|
| DOI | 10.1007/s00894-017-3318-8 |
| Pubmed ID | |
| Authors |
Siba Shanak, Ozlem Ulucan, Volkhard Helms |
| Abstract |
DNA methylation plays a major role in organismal development and the regulation of gene expression. Methylation of cytosine bases and the cellular roles of methylated cytosine in eukaryotes are well established, as well as methylation of adenine bases in bacterial genomes. Still lacking, however, is a general mechanistic understanding, in structural and thermodynamic terms, of how proteins recognize methylated DNA. Toward this aim, we present the results of molecular dynamics simulations, alchemical free energy perturbation, and MM-PBSA calculations to explain the specificity of the R.DpnI enzyme from Streptococcus pneumonia in binding to adenine-methylated DNA with both its catalytic and winged-helix domains. We found that adenine-methylated DNA binds more favorably to the catalytic subunit of R.DpnI (-4 kcal mol(-1)) and to the winged-helix domain (-1.6 kcal mol(-1)) than non-methylated DNA. In particular, N6-adenine methylation is found to enthalpically stabilize binding to R.DpnI. In contrast, C5-cytosine methylation entropically favors complexation by the MBD domain of the human MeCP2 protein with almost no contribution of the binding enthalpy. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 20 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 7 | 35% |
| Student > Doctoral Student | 2 | 10% |
| Researcher | 2 | 10% |
| Student > Ph. D. Student | 2 | 10% |
| Student > Bachelor | 1 | 5% |
| Other | 2 | 10% |
| Unknown | 4 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 7 | 35% |
| Agricultural and Biological Sciences | 2 | 10% |
| Chemistry | 2 | 10% |
| Nursing and Health Professions | 1 | 5% |
| Immunology and Microbiology | 1 | 5% |
| Other | 3 | 15% |
| Unknown | 4 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 April 2017.
All research outputs
#20,412,387
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Outputs from Journal of Molecular Modeling
#636
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#269,225
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Outputs of similar age from Journal of Molecular Modeling
#20
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