Sequence and temperature effect on hydrogen bond disruption in DNA determined by a statistical analysis

Area of Science:

• Biophysics
• Computational Biology
• Molecular Biophysics

Background:

• DNA stability is crucial for biological functions.
• Understanding thermal disruption of DNA base pairs is key to DNA mechanics.
• Previous models lacked detailed sequence-dependent thermal disruption profiles.

Purpose of the Study:

• To calculate temperature-dependent hydrogen bond disruption profiles in DNA polymers.
• To investigate the sequence dependence of base pair opening.
• To compare theoretical predictions with experimental observations.

Main Methods:

• Modified self-consistent phonon approximation theory.
• Calculation of temperature-dependent interbase hydrogen bond disruption probabilities.
• Analysis of six base pair repeating sequence B-DNA polymers with varying GC/AT ratios.

Main Results:

• Calculated probabilities show no sequence dependence at premelting temperatures.
• Sequence dependence becomes significant near DNA melting temperatures.
• Multiphasic critical transitions, including localized and non-localized base pair opening, were identified.
• Transition midpoint temperatures correlate linearly with guanine-cytosine content.

Conclusions:

• The modified self-consistent phonon approximation theory effectively models DNA H-bond disruption.
• The theory explains sequence-dependent thermal stability and base pair opening phenomena.
• Findings align with experimental observations of DNA melting and stability.