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Related Concept Videos

DNA as a Genetic Template02:05

DNA as a Genetic Template

Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
DNA as a Genetic Template02:05

DNA as a Genetic Template

Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
Nucleic Acid Structure01:25

Nucleic Acid Structure

The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...
The DNA Helix01:16

The DNA Helix

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The DNA Helix01:07

The DNA Helix

Deoxyribonucleic acid, or DNA, is the genetic material responsible for passing traits from generation to generation in all organisms and most viruses. DNA is composed of two strands of nucleotides that wind around each other to form a spring-like structure called a double helix. However, the double helix is not perfectly symmetrical. Instead, there are regularly occurring grooves in the structure. The major groove occurs where the sugar-phosphate backbones are relatively far apart. This space...
The DNA Helix01:16

The DNA Helix

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Analyzing and Building Nucleic Acid Structures with 3DNA
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A nonlinear dynamic model of DNA with a sequence-dependent stacking term.

Boian S Alexandrov1, Vladimir Gelev, Yevgeniya Monisova

  • 1Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.

Nucleic Acids Research
|March 7, 2009
PubMed
Summary

A new DNA model accurately predicts melting behavior for homogenous and periodic sequences. This advance aids studying genomic regions like CpG islands and disease-related repeats.

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Area of Science:

  • Biophysics
  • Genomics
  • Computational Biology

Background:

  • Accurate modeling of double-stranded DNA melting and breathing dynamics remains challenging, particularly for homogenous and periodic sequences.
  • Existing models fail to predict melting temperatures for sequences with large deviations from additive thermodynamic contributions.
  • Methods for analyzing DNA breathing dynamics in repetitive and GC/AT-rich regions are currently lacking, despite their prevalence in vertebrate genomes.

Purpose of the Study:

  • To extend the nonlinear Peyrard-Bishop-Dauxois (PBD) model to incorporate sequence-dependent stacking interactions.
  • To develop a model capable of accurately describing the melting behavior of homogenous and periodic DNA sequences.
  • To facilitate thermodynamic and dynamic simulations of critical genomic regions.

Main Methods:

  • Extension of the nonlinear Peyrard-Bishop-Dauxois (PBD) model with a sequence-dependent stacking term.
  • Collection of melting data for various DNA oligonucleotides.
  • Application of Monte Carlo simulations to determine force constants for 10 distinct dinucleotide steps.

Main Results:

  • The extended PBD model accurately describes the melting behavior of homogenous and periodic DNA sequences.
  • Force constants were established for dinucleotide steps including CG, CA, GC, AT, AG, AA, AC, TA, GG, and TC.
  • Experimental and simulation data revealed that GG/CC dinucleotide stacking is significantly less stable than that in GC/CG and CG/GC steps.

Conclusions:

  • The enhanced PBD model provides a more accurate description of DNA melting dynamics, especially for challenging sequences.
  • This model enables improved thermodynamic and dynamic simulations of genomic regions.
  • The findings are crucial for understanding CpG islands and disease-related repeats within genomes.