Interaction preferences between protein side chains and key epigenetic modifications 5-methylcytosine, 5-hydroxymethycytosine and N⁶-methyladenine.

ABSTRACT: Covalent modifications of standard DNA/RNA nucleobases affect epigenetic regulation of gene expression by modulating interactions between nucleic acids and protein readers. We derive here the absolute binding free energies and analyze the binding modalities between key modified nucleobases 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and N⁶-methyladenine (m⁶A) and all non-prolyl/non-glycyl protein side chains using molecular dynamics simulations and umbrella sampling in both water and methanol, the latter mimicking the low dielectric environment at the dehydrated nucleic-acid/protein interfaces. We verify the derived affinities by comparing against a comprehensive set of high-resolution structures of nucleic-protein complexes involving 5mC. Our analysis iden

SUBMITTER: Hajnic M 

PROVIDER: S-EPMC9666514 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature