Flexibility of short-strand RNA in aqueous solution as revealed by molecular dynamics simulation:are A′-RNA and A-RNA distinct conformational structures?

We use molecular dynamics simulations to compare the conformational structure and dynamics of a 21-base pair RNA sequence initially constructed according to the canonical A-RNA and A'-RNA forms in the presence of counterions and explicit water. Our study aims to add a dynamical perspective to the solid-state structural information that has been derived from X-ray data for these two characteristic forms of RNA. Analysis of the three main structural descriptors commonly used to differentiate between the two forms of RNA namely major groove width, inclination and the number of base pairs in a helical twist over a 30 ns simulation period reveals a flexible structure in aqueous solution with fluctuations in the values of these structural parameters encompassing the range between the two crystal forms and more. This provides evidence to suggest that the identification of distinct A-RNA and A'-RNA structures, while relevant in the crystalline form, may not be generally relevant in the context of RNA in the aqueous phase. The apparent structural flexibility observed in our simulations is likely to bear ramifications for the interactions of RNA with biological molecules (e.g. proteins) and non-biological molecules (e.g. non-viral gene delivery vectors)

Protein-facilitated base flipping in DNA by cytosine-5-methyltransferase

DNA methylation, various DNA repair mechanisms, and possibly early events in the opening of DNA as required for transcription and replication are initiated by flipping of a DNA base out of the DNA double helix. The energetics and structural mechanism of base flipping in the presence of the DNA-processing enzyme, cytosine 5-methyltransferase from HhaI (M.HhaI), were obtained through molecular dynamics based upon free-energy calculations. Free-energy profiles for base flipping show that, when in the closed conformation, M.HhaI lowers the free-energy barrier to flipping by 17 kcal/mol and stabilizes the fully flipped state. Flipping is shown to occur via the major groove of the DNA. Structural analysis indicates that flipping is facilitated by destabilization of the DNA double-helical structure and substitution of DNA base-pairing and base-stacking interactions with DNA–protein interactions. The fully flipped state is stabilized by DNA–protein interactions that are enhanced upon binding of coenzyme. This study represents an atomic detail description of the mechanism by which a protein facilitates specific structural distortion in DNA

Low-frequency normal mode in DNA HhaI methyltransferase and motions of residues involved in the base flipping

The results of normal-mode analyses are in accord with the proposal that a low-frequency motion of the HhaI methyltransferase enzyme is responsible for base flipping in bound DNA. The vectors of the low-frequency normal mode of residues Ser-85 and Ile-86 point directly to the phosphate and ribose moieties of the DNA backbone near the target base in position to rotate the dihedral angles and flip the base out of the DNA duplex. The vector of residue Gln-237 on the major groove is in the proper orientation to assist base separation. Our results favor the major groove pathway and the protein active process in base flipping

Additional file 1: of CHiCAGO: robust detection of DNA looping interactions in Capture Hi-C data

The mathematical specification of the CHiCAGO algorithm. (PDF 304 kb

Additional file 3: of CHiCAGO: robust detection of DNA looping interactions in Capture Hi-C data

The CHiCAGO R package tutorial. (PDF 946 kb