Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Structure-function studies of DNA damage using ab initio quantum mechanics and molecular dynamics simulation

J Miller1, K Miaskiewicz, R Osman

  • 1Biology and Chemistry Department, Pacific Northwest Laboratory, Richland, Washington 99352.

Annals of the New York Academy of Sciences
|July 29, 1994
PubMed
Summary

Integrated modeling reveals how ring-saturated thymine lesions distort DNA. Conformational preferences of these DNA base lesions impact DNA structure, influencing recognition by enzymes like endonuclease III.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

The importance of arginine 102 for the substrate specificity of Escherichia coli malate dehydrogenase.

Biochemical and biophysical research communications·1992
Same author

High-efficiency gene transfer into cardiac myocytes.

Nucleic acids research·1992
Same author

Brain-derived neurotrophic factor augments rotational behavior and nigrostriatal dopamine turnover in vivo.

Proceedings of the National Academy of Sciences of the United States of America·1992
Same author

Differentiated practice: a three-dimensional model.

Nursing management·1992
Same author

Use of unlicensed assistive personnel in acute care settings.

The Journal of nursing administration·1992
Same author

Effect of a human immunodeficiency virus protease inhibitor on human monocyte function.

AIDS research and human retroviruses·1992

Area of Science:

  • Biochemistry
  • Computational Chemistry
  • Molecular Biology

Background:

  • Pyrimidine base lesions, specifically ring-saturated types, are critical DNA damage products.
  • Understanding the structural consequences of these lesions is vital for DNA repair mechanisms.
  • Previous studies have indicated potential structural alterations but lacked integrated computational approaches.

Purpose of the Study:

  • To illustrate an integrated modeling approach combining quantum-chemical calculations and molecular dynamics simulations.
  • To investigate the conformational preferences of ring-saturated pyrimidine base lesions.
  • To determine the impact of these lesions on DNA structure and their implications for enzyme recognition.

Main Methods:

  • Quantum-chemical calculations were performed on isolated pyrimidine base lesions.

Related Experiment Videos

  • Molecular dynamics simulations were conducted on a DNA dodecamer containing specific thymine lesions.
  • Comparative analysis of DNA structures with and without lesions was performed.

    • Main Results:

    • Electronic structure calculations identified strong conformational preferences in lesions due to substituent interactions.
    • A significant distortion of DNA structure was predicted when thymine's methyl group adopts an axial orientation (e.g., thymine glycol).
    • Molecular dynamics simulations confirmed these distortions in a DNA dodecamer model.

    Conclusions:

    • The study demonstrates the utility of integrated computational modeling for understanding DNA lesion structures.
    • Ring-saturated thymine lesions, like thymine glycol, can induce substantial DNA distortions.
    • These structural changes are relevant for the recognition of DNA damage by repair enzymes such as endonuclease III.