Mutagenesis and modeling

Ira Ropson iropson at bcmic.hmc.psu.edu
Mon Feb 24 12:00:15 EST 1997


Hello world,

I have made several single amino acid substitutions using site-directed
mutagenesis for a protein for which a good crystal structure is
available. I would like to use molecular modeling techniques to compare
the relative stability of these proteins in silico to the measurements
I have made in vitro using denaturants. Several of these measured
stabilities have been unexpected given the structural location and
relative hydrophobicity of the substitutions I made. I suspect that
simple intuition is not sufficient to explain the results, and I need
to do some molecular modeling/molecular dynamics calculations to make
sense of these numbers. Is this a practical idea? How should I go about
it? Are there any reviews that are focused on this issue? How
successful have these kinds of predictions been in the past? Is there
any particuIar software packages that would be very useful for this
purpose? I currently have a Silicon Graphics Indigo (R3000) with the
insightII/Discover package along with Sculpt for the PowerMac, and not
a whole lot of money. I would greatly appreciate any comments.

Thanks,
Ira Ropson
iropson at bcmic.hmc.psu.edu
If I had time for a fancy Sig file I probably wouldn't have a job.



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