Journal of Physical Chemistry B
Journal of Physical Chemistry B
5 years ago

All-Atom MD Predicts Magnesium-Induced Hairpin in Chemically Perturbed RNA Analog of F10 Therapeutic

All-Atom MD Predicts Magnesium-Induced Hairpin in Chemically Perturbed RNA Analog of F10 Therapeutic
Freddie R. Salsbury, William H. Gmeiner, Ryan L. Melvin
Given their increasingly frequent usage, understanding the chemical and structural properties which allow therapeutic nucleic acids to promote the death of cancer cells is critical for medical advancement. One molecule of interest is a 10-mer of FdUMP (5-fluoro-2′-deoxyuridine-5′-O-monophosphate) also called F10. To investigate causes of structural stability, we have computationally restored the 2′ oxygen on each ribose sugar of the phosphodiester backbone, creating FUMP[10]. Microsecond time-scale, all-atom, simulations of FUMP[10] in the presence of 150 mM MgCl2 predict that the strand has a 45% probability of folding into a stable hairpin-like secondary structure. Analysis of 16 μs of data reveals phosphate interactions as likely contributors to the stability of this folded state. Comparison with polydT and polyU simulations predicts that FUMP[10]’s lowest order structures last for one to 2 orders of magnitude longer than similar nucleic acid strands. Here we provide a brief structural and conformational analysis of the predicted structures of FUMP[10], and suggest insights into its stability via comparison to F10, polydT, and polyU.

Publisher URL: http://dx.doi.org/10.1021/acs.jpcb.7b04724

DOI: 10.1021/acs.jpcb.7b04724

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.