Complementary base pair interactions between different rare tautomers of the second-generation artificial genetic...

Area of Science:

• Biochemistry
• Computational Chemistry
• Molecular Biology

Background:

• The stability and functionality of semisynthetic DNA depend on the specific interactions between its base pairs.
• Understanding these interactions is crucial for developing novel DNA technologies and therapeutics.
• Artificial nucleobases offer new possibilities for expanding the genetic alphabet.

Purpose of the Study:

• To investigate the base pairing interactions of eight second-generation artificial nucleobases.
• To evaluate the influence of rare tautomeric conformations on base pair stability.
• To determine the energetic favorability of different base pairing configurations for semisynthetic DNA duplexes.

Main Methods:

• Utilizing a dispersion-corrected density functional theoretic method to model base pair interactions.
• Analyzing complementary base pairing involving rare tautomeric forms of artificial nucleobases.
• Calculating binding energies and thermodynamic properties of various base pairs.

Main Results:

• Two hydrogen-bonded complementary base pairs exhibited more negative binding energies compared to three hydrogen-bonded pairs.
• However, the two hydrogen-bonded pairs were found to be endothermic.
• The study indicates a preference for three hydrogen-bonded base pairs in stable semisynthetic DNA duplexes.

Conclusions:

• The nature of complementary base pairing significantly impacts the stability of semisynthetic DNA.
• While stronger binding can be achieved with fewer hydrogen bonds, thermodynamic stability favors more hydrogen bonds.
• These findings guide the design of stable and functional artificial DNA systems.