The UNSW Medicine & Health's EMBL Australia Node in Single Molecule Science joined forces to demystify the complicated mechanisms governing how quickly two matching strands ofDNA can come together. Their work is published in a journal.
The idea that how quickly the strands hybridize is determined by the initial contact is hypothesizing. This theory has never been proven due to the complexity of the topic.
There are many pathways through which strands can bind together. In an instant, a fully hybridized duplex is not possible. Only a few base pairs will spontaneously join. A nucleating event is what Associate Professor Lawrence Lee described as a nucleating event.
If we only knew how many nucleating interactions there were, and how stable they were, could we predict hybridization rates? He said that the answer was yes.
The research team used a mathematical formula to measure against their experimental observations against the model.
A/ Prof Lee says simplicity was important to their model.
Predicting is no longer possible if a mathematical model has too many parameters. He said that the key difference to previous attempts was that the model had few parameters and was tested against DNA that shouldn't form secondary structures.
Secondary structures are formed when the strands fold onto themselves.
If this initial small interaction is stable enough, it will go from there to a very fast zipping up of the DNA strands. If you have more nucleating states, then the DNA should hybridize faster.
Our understanding of biological systems could be improved by this discovery. Predicting or controlling the rate of hybridisation could help to refine or expand the utility of the technology. Researchers can change the number and stability of nucleation interactions with this new understanding. Changing the reaction temperature, DNA sequence, and ionic strength of the solution can be done to achieve this.
Because we are measuring the binding and unbinding of DNA to individual molecule, we can generate high resolution images. It can take a while to get the data. "If we could rationally design sequence for DNA paint so that it can bind more rapidly, then we could reduce the acquisition time for super-resolution images."
More information: Sophie Hertel et al, The stability and number of nucleating interactions determine DNA hybridization rates in the absence of secondary structure, Nucleic Acids Research (2022). DOI: 10.1093/nar/gkac590 Journal information: Nucleic Acids Research
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