Monday, June 11, 2012

Altritol-RNA Duplex at 1.96Å and P5abc RNA Folding Pathway

How Does Hydroxyl Introduction Influence the Double Helical Structure: The Stabilization of an Altritol Nucleic Acid:Ribonucleic Acid Duplex
Margriet Ovaere, Jiri Sponer, Judit E. Sponer, Piet Herdewijn, Luc Van Meervelt
NAR (2012), XX, 1-11

Altritol Nucleic Acids (ANA) are those whose ribose sugar has been modified to have and additional methylene group between the O4' and C1' atoms in the sugar of an RNA:

A duplex can then be made between RNA strands and ANA strands and the results for the nice duplex elucidated with X-Ray crystallography at 1.96 Ångstrom resolution are reported by Ovaere and coworkers. The structure can be found at the Protein Data Bank (PDB) under PDB_ID:3OK2.

One can compare the RNA-ANA, to plain old RNA, an RNA-LNA duplex, and a LNA-LNA duplex as illustrated in the following picture.

Folding Path  of P5abc RNA  Involves Direct Coupling of  Secondary and Tertiary Structures
Eda Koculi, Samuel S. Cho, Ravi Desai, D. Thirumalai, and Sarah A. Woodson
NAR (2012), XX, 1-11

Once again the collaboration of Sarah Woodson with one of her former graduate students brings out beautiful results to further our understanding of RNA folding.

In this case the energy diagram talks by itself.

Thursday, June 7, 2012

Nano-DNA Tech., Femtosecond X-ray of the Future, and Yet Another Small-Molecule Detector Made of DNA.

In this week's Chemical and Engineering News three reviews concerned nucleic acids. A first review claims that a group at Harvard Medical School has a more effective technique (faster) than Ned Seeman's to produce DNA shapes. A second review is about computer simulations which predict that data can be extracted from an spectroscopy, previously thought of as destructive, and a third review concerns yet another technique to use DNA to detect small ligands.

Complex Shapes Self-Assembled from Single-Stranded DNA Tiles
Bryan Wei, Mingjie Dai, and Peng Yin
Nature (2012), 485, 623-626

The authors are all part of an institute called, "Wyss Institute for Biologically Inspired Engineering", which seems to be a newish institute at Harvard, probably started in 2008, and which got a $125 million dollar donation from Hansjörg Wyss, a billionaire who owns a company called Synthes which makes implants and various medical devices. They claim that up to now the process of engineering DNA shapes is done using "a long scaffold strand which is folded by hundreds of short auxiliary strands into a complex shape", and their method uses the simplest tile form, they call it an SST (single-stranded tile). Surprisingly they reference Luc Jaeger's work (who has developed the single-stranded assembly technique for RNA's since at least 1996, called RNA Tectonics)  just in passing. As part of their results they show an AFM image of the assembled 2D DNA-shapes:

Potential for Biomolecular Imaging with Femtosecond X-ray Pulses
Richard Neutze, Remco Wouts, David Van der Spoel, Edgar Weckert, Janos Hajdu
Nature (2000), 406, 752-757

This oldish paper was highlighted because what they proposed in 2000 has now become a reality.
If one is interested ever in showing examples of the power of theory, and computational modeling has on future achievement in science, this is an excellent example. In the experimental paper which proves the predictions (Science, (2012), 337, 362-364), they are using a so-called Serial Femtosecond Crystallography (SFX) which allows them to obtain a 1.9 Ångstrom resolution structure of an enzyme called lysozyme, from microcrystals which would be useless for conventional X-ray crystallography, an using a coherent X-ray imaging instrument (LCLS) form the Stanford Linear Accelerator Center(SLAC):

The PDB  structures have  the following accession codes:
4ET8, 4ET9, 4ETA, 4ETB, 4ETC, 4ETD, 4ETE.