Distributions of Bubble Lifetimes and Bubble Lengths in DNA

TL;DR

This study uses molecular dynamics simulations to analyze how DNA sequence composition influences bubble lifetimes and lengths, revealing that AT-rich regions favor longer, more frequent bubbles, with the extended model predicting even more extensive bubbling.

Contribution

It introduces sequence-dependent thresholds in DNA bubble modeling and compares PBD and extended ePBD models to better understand bubble dynamics.

Findings

Bubble lifetime decreases with increasing GC content.

Longer bubbles are more common in AT-rich sequences.

Extended model predicts more and longer-lived bubbles.

Abstract

We investigate the distribution of bubble lifetimes and bubble lengths in DNA at physiological temperature, by performing extensive molecular dynamics simulations with the Peyrard-Bishop-Dauxois (PBD) model, as well as an extended version (ePBD) having a sequence-dependent stacking interaction, emphasizing the effect of the sequences' guanine-cytosine (GC)/adenine-thymine (AT) content on these distributions. For both models we find that base pair-dependent (GC vs AT) thresholds for considering complementary nucleotides to be separated are able to reproduce the observed dependence of the melting temperature on the GC content of the DNA sequence. Using these thresholds for base pair openings, we obtain bubble lifetime distributions for bubbles of lengths up to ten base pairs as the GC content of the sequences is varied, which are accurately fitted with stretched exponential functions. We find that for both models the average bubble lifetime decreases with increasing either the bubble length or the GC content. In addition, the obtained bubble length distributions are also fitted by appropriate stretched exponential functions and our results show that short bubbles have similar likelihoods for any GC content, but longer ones are substantially more likely to occur in AT-rich sequences. We also show that the ePBD model permits more, longer-lived, bubbles than the PBD system.