Dynamics of the Watson-Crick to Hoogsteen transition in DNA
The identification of the double-helix structure of DNA was one of the most important discoveries of the 20th century, for which Francis Crick, James Watson, and Maurice Wilkins were awarded the 1962 Nobel Prize. However, recent experiments1 have shown that the Watson-Crick base pairing motif is not the only one that is significant in physiological DNA. Another structure, proposed by Karst Hoogsteen in ???,2 also plays a role. We have simulated the transition between the Watson-Crick and Hoogsteen base pairing motifs, in order to better understand its mechanism and kinetics.
The identification of the double-helix structure of DNA was one of the most important discoveries of the 20th century, for which Francis Crick, James Watson, and Maurice Wilkins were awarded the 1962 Nobel Prize. However, recent experiments1 have shown that the Watson-Crick base pairing motif is not the only one that is significant in physiological DNA. Another structure, proposed by Karst Hoogsteen in ???,2 also plays a role. We have simulated the transition between the Watson-Crick and Hoogsteen base pairing motifs, in order to better understand its mechanism and kinetics.
The exact importance of these base pairs in the Hoogsteen motif is still unknown. However, some base pairs may spend as much as 1% of their time in the Hoogsteen state, and that’s enough that it could be biologically important. Furthermore, stabilizing the Hoogsteen conformation might also be a new aim for drugs, such as antivirals.
What’s the difference between Hoogsteen and Watson-Crick? Recall that DNA consists of four base pairs (A, T, C, and G), which can be split into two groups: purines (A and G) and pyrimidines (T and C). The pyrimidines have a six-membered ring, whereas the purines have both a five-membered ring and a six-membered ring. Every base pair is between one purine and one pyrimidine.
In the Watson-Crick motif, the