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

Sequence-dependent dynamics of TATA-Box binding sites

D Flatters1, R Lavery

  • 1Laboratoire de Biochimie Théorique, CNRS UPR 9080, Institut de Biologie Physico-Chimique, Paris 75005, France.

Biophysical Journal
|July 2, 1998
PubMed
Summary
This summary is machine-generated.

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

Identifying promising druggable binding sites and their flexibility to target the receptor-binding domain of SARS-CoV-2 spike protein.

Computational and structural biotechnology journal·2023
Same author

Age adjusted D-dimer in the Belfast Health and Social Care Trust: A retrospective study.

The Ulster medical journal·2018
Same author

Improving the treatment of coarse-grain electrostatics: CVCEL.

The Journal of chemical physics·2016
Same author

Energetic and conformational aspects of A:T base-pair opening within the DNA double helix.

Chemphyschem : a European journal of chemical physics and physical chemistry·2013
Same author

A Mechanism for RecA-Promoted Sequence Homology Recognition and Strand Exchange Between Single-Stranded DNA and Duplex DNA, via Triple-Helical Intermediates.

Journal of biomolecular structure & dynamics·2012
Same author

Conformational analysis of nucleic acids revisited: Curves+.

Nucleic acids research·2009

Molecular dynamics simulations reveal that minor DNA sequence changes significantly alter DNA structure and dynamics. These alterations impact TATA-box binding protein interactions, explaining reduced binding affinity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Computational Biology

Background:

  • The TATA-box binding protein (TBP) is crucial for transcription initiation in eukaryotes.
  • DNA sequence and structure influence protein-DNA interactions and binding affinity.
  • Previous studies indicated a related DNA oligomer possesses a strong TBP binding site.

Purpose of the Study:

  • To investigate the molecular basis of differential TATA-box binding protein (TBP) binding affinity.
  • To analyze the structural and dynamic consequences of specific base pair mutations in a DNA oligomer.
  • To assess the utility of molecular dynamics (MD) simulations in understanding protein-nucleic acid recognition.

Main Methods:

  • Conducted two nanosecond-length molecular dynamics (MD) simulations.

Related Experiment Videos

  • Utilized explicit solvent and counterions in simulations.
  • Avoided truncation of electrostatic interactions during simulations.

    • Main Results:

    • The DNA oligomer d(GCGTAAAAAAAACGC)2, with a weak TBP binding site, exhibited distinct structural and dynamic behavior compared to a related oligomer with a strong binding site.
    • Two specific base pair mutations correlated with significant changes in time-averaged structure and dynamic properties across the entire DNA oligomer.
    • Observed changes in DNA structure and dynamics were consistent with experimentally reported decreases in TBP binding and functional activity.

    Conclusions:

    • MD simulations with explicit solvent and counterions provide powerful insights into indirect protein-nucleic acid recognition mechanisms.
    • Subtle alterations in DNA sequence can lead to substantial changes in DNA conformation and dynamics, affecting protein binding.
    • Computational approaches are valuable for elucidating the complex interplay between DNA structure, dynamics, and protein recognition.