DETERMINATION OF SOLUTION STRUCTURES FROM NMR

Project Details

Description

DESCRIPTION: High resolution NMR has
become an important tool for determination of solution structures of
proteins and nucleic acids, but there are still important questions to be
resolved about how precise and accurate these structures are. The research
proposed here focuses on careful comparisons of calculated and observed
2D-correlated nuclear Overhauser effect spectroscopy (NOESY) as a means of
analyzing and improving structures. The key elements are: (1) the use of
gradient-based refinement techniques to improve agreement between
calculated and observed spectra; (2) the development and calibration of
models for molecular tumbling and internal motion that will lead to more
reliable estimates of NOESY intensities; (3) molecular dynamics simulations
of proteins in water to help design internal motion models and to develop
simulated data against which refinement methods can be tested; and (4) the
incorporation of direct matrix inversion techniques in the refinement
scheme, providing for smoothing of the data and improved estimation of weak
peaks. Two additional projects will be pursued that should also help to make NMR
refinement a more robust and accurate process. First, systematic search
procedures at the di- and tri-peptide level will be explored as a means of
generating better distance bounds, of making reliable stereospecific
assignments, and of detecting inconsistencies in experimental data.
Second, empirical models for conformation-dependent chemical shifts will be
developed and tested against a large database of experimental information,
and the extent to which refinement against such data can be used to improve
structures will be tested. The techniques developed here will be used to refine solution structures of
plastocyanin, a "zinc finger" peptide, and two oligonucleotides,
d(ATATATAUAT)2 and d(CAUAUAUAUG)2 using experimental data provided by Peter
Wright and Tom James. The computer codes incorporating these refinement
techniques will be assembled into a portable and documented package and
made available to the NMR community.
StatusFinished
Effective start/end date4/1/917/31/17

Funding

  • National Institutes of Health: $230,715.00
  • National Institutes of Health: $281,550.00
  • National Institutes of Health
  • National Institutes of Health: $136,412.00
  • National Institutes of Health
  • National Institutes of Health: $79,861.00
  • National Institutes of Health: $223,211.00
  • National Institutes of Health: $281,550.00
  • National Institutes of Health: $231,307.00
  • National Institutes of Health: $229,433.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $274,934.00
  • National Institutes of Health: $227,139.00
  • National Institutes of Health: $231,307.00
  • National Institutes of Health: $161,719.00
  • National Institutes of Health: $181,647.00
  • National Institutes of Health: $209,238.00
  • National Institutes of Health: $205,973.00
  • National Institutes of Health
  • National Institutes of Health: $231,750.00
  • National Institutes of Health: $171,977.00
  • National Institutes of Health: $281,550.00
  • National Institutes of Health
  • National Institutes of Health: $223,061.00
  • National Institutes of Health: $77,102.00

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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