Project Details

Description

The objectives of this research are to design new NMR experiments and
computer software needed for refining the solution structures of small
proteins and for determining the structures of proteins which are too large
(10,000 - 25,000 MW) to be solved with existing methods. The work will
expand upon recent advances in 1H-detection of 13C and 15N magnetic
resonance applied to two-dimensional (2D-), 3D-, and 4D-NMR spectroscopy,
triple-resonance assignments in proteins. New multidimensional- (MD-) NMR
experiments will be designed which provide more precise NMR structural
parameters than available with existing technology. In particular, we will
design methods for accurate measurements of homonuclear and heteronuclear
vicinal coupling constants in proteins. We will develop an approach for
protein structure determination involving measurements of multiple vicinal
couplings for each phi, psi, and chi1 dihedral angle in a small protein.
These methods will provide better determination of local backbone and side
chain conformation than is available with existing techniques. MD-NMR
experiments will be designed which use PFG'S for suppression of H2O solvent
signals in a single scan and for avoiding saturation transfer problems at
neural pH. PFG's will also be used to overcome the dynamic range problems
encountered in 1H-detected heteronuclear NMR of proteins at natural isotope
abundance. This new technology will be applied for structural studies of
growth factors involved in the molecular basis of cancer and wound healing,
including proteins too large to study with existing methods. It will
greatly enhance the applicability of NMR as a tool for rational drug design
and protein engineering.
StatusFinished
Effective start/end date2/1/923/31/03

Funding

  • National Institutes of Health
  • National Institutes of Health: $211,615.00
  • National Institutes of Health: $238,248.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $179,502.00
  • National Institutes of Health: $136,511.00
  • National Institutes of Health: $199,940.00
  • National Institutes of Health

ASJC

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

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