Please use this identifier to cite or link to this item: doi:10.22028/D291-30520
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Title: Methylation-targeted specificity of the DNA binding proteins R.DpnI and MeCP2 studied by molecular dynamics simulations
Author(s): Shanak, Siba
Ulucan, Ozlem
Helms, Volkhard
Language: English
Title: Journal of molecular modeling
Volume: 23
Issue: 5
Publisher/Platform: Springer
Year of Publication: 2017
Publikation type: Journal Article
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.
DOI of the first publication: 10.1007/s00894-017-3318-8
URL of the first publication:
Link to this record: hdl:20.500.11880/28896
ISSN: 0948-5023
Date of registration: 20-Mar-2020
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Volkhard Helms
Collections:Die Universitätsbibliographie

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