Article on Watson-Crick to Hoogsteen transition in DNA published
When I first started my post-doc in Amsterdam, I browsed around for interesting systems that might be suitable to study with transition path sampling. I came across a very interesting paper in Nature that showed that, in addition to the well-known Watson-Crick structure, parts of DNA could transiently take on the Hoogsteen base pairing motif. The transition between Watson-Crick and Hoogsteen motifs seemed very appropriate for transition path sampling. I brought this idea to a colleague of mine in Amsterdam, Jocelyne Vreede, who had more experience with biomolecular simulation than I did. She was also interested, and so we started playing with this idea as a small side project.
Since it was a side project for both of us, it took a long time for it to be ready for publication. However, the results of our work have finally been published in Nucleic Acids Research. Overall, we look at two classes of transitions: “inside” transitions, where the transition from Watson-Crick to Hoogsteen bonding occurs without the relevant bases leaving the double helix, and “outside” transitions, where a base exits the double helix (opening to solvent) before returning in the Hoogsteen conformation.
Although much previous work had focused on the inside transition, our work shows that this transition is much more likely to occur via the outside mechanism. The extent of the importance of Hoogsteen base pairing is still only partially understood, but our insight may help other researchers understand some forms of DNA transcription, some antiviral drugs, or other aspects of fundamental biomolecular science.
David W.H. Swenson
RESEARCH · DNA-BASEROLLING paper