LICHTARGE@SUMEX-AIM.ARPA (Olivier Lichtarge) (09/23/86)
I will be presenting my thesis defense in biophysics Thursday
September 25 in the chemistry Gazebo, starting at 2:15.
Solution Structure Determination of Beta-endorphin by NMR
and
Validation of Protean: a Structure Generation Expert System
Solution structure determination of proteins by Nuclear Magnetic
Resonance involves two steps. First, the collection and interpretation
of data, from which the secondary structure of a protein is
characterized and a set of constraints on its tertiary structure
identified. Secondly, the generation of 3-dimensional models of the
protein which satisfy these constraints. This thesis presents works in
both these areas: one and two-dimensional NMR techniques are applied
to study the conformation of @g(b)-endorphin; and Protean, a new
structure generation expert system is introduced and validated by
testing its performance on myoglobin.
It will be shown that @g(b)-endorphin is a random coil in water. In
a 60% methanol and 40% water mixed solvent the following changes take
place: an @g(a)-helix is induced between residues 14 and 27, and a
salt bridge forms between Lysine28 and Glutamate31, however, there
still exists no strong evidence for the presence of tertiary structure.
The validation of Protean establishes it as an unbiased and accurate
method of generating a representative sampling of all the possible
conformations which satisfy the experimental data. At the solid level,
the precision is good enough to clearly define the topology of the
protein. An analysis of Protean's performance using data sets of
dismal to ideal quality permits us to define the limits of the
precision with which a structure can be determined by this method.
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