How proton transfer affects the helical parameters in DNA:DNA microhelices.

Area of Science:

• Biochemistry
• Molecular Biology
• Computational Chemistry

Background:

• Proton transfer reactions are fundamental in life sciences and linked to DNA replication errors.
• Previous studies focused on proton transfer mechanisms, but structural geometric changes were unexplored.

Purpose of the Study:

• To investigate the structural and geometrical alterations induced by double proton transfer (DPT) in DNA.
• To analyze the impact of DPT on helical parameters and base pair stability in DNA microhelices.

Main Methods:

• Utilized the M06-2X Density Functional Theory (DFT) method for calculations.
• Optimized Watson-Crick (WC) base pairs in both single nucleoside models and three-nucleoside DNA microhelices.
• Considered canonical and tautomeric forms within A-type and B-type helical DNA microhelices.

Main Results:

• The purine/pyrimidine ring in the keto form exhibited greater deformability compared to the enol form.
• Double proton transfer significantly deformed helical and backbone parameters in DNA microhelices.
• Weaker WC base pairing was observed in mixed microhelices compared to isolated nucleobases.

Conclusions:

• Double proton transfer induces significant structural deformations in DNA microhelices, impacting helical parameters.
• The keto tautomeric form is more prone to deformation, potentially influencing DNA stability and mutation processes.
• The combined effects of base pairing and DPT complicate proton transfer dynamics within microhelical DNA structures.