DNA STABILITY AND FLEXIBILITY: A THERMODYNAMIC STUDY

Project Details

Description

Our goal is to develop a thermodynamic library of the sequence-dependent
molecular forces that dictate and control DNA secondary structures in
solution. These data will be used to predict the sequence-dependent
structural preferences of local domains along the DNA polymer chain. Such
a predictive ability will allow us to search for correlations between
specific structural features and particular functional roles. The thermodynamic data required to achieve this predictive power will be
obtained from calorimetric studies on selected oligomeric and polymeric DNA
duplexes. Specifically, relative stabilities (DeltaG),
temperature-dependent flexibilities (DeltaH, DeltaCp), and melting
cooperativities (DeltaHv.H./DeltaHcal.) will be determined as a function of
base sequence for fully-bonded duplexes, hairpins, cruciform-like
structures, bulge loops, internal loops, and duplexes containing
selectively modified bases. Significantly, calorimetry represents the only
experimental method by which the relevant thermodynamic data can be
obtained in a direct and model-independent manner. The proposed studies will provide us with complete sequence-dependent
thermodynamic profiles for each secondary structural feature. Such data
will permit the construction of a phase diagram in which DNA secondary
structural preferences are mapped as a function of base sequence and
temperature. Considering the potential role of conformational heterogeneity as a
mechanism for selective, local control of events such as protein-nucleic
acid interactions, drug-DNA binding, gene expression, and DNA packing, an
ability to predict local conformational prefernces in DNA polymers is of
the utmost importance. The calorimetric experiments described in this
proposal represent a continuation of our efforts to obtain the
thermodynamic data required to achieve this predictive ability.
StatusFinished
Effective start/end date12/31/893/31/00

Funding

  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Genetics
  • Polymers and Plastics
  • Spectroscopy

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