Dear graduate students and postdocs,
I talked on Friday to Suzanne Walker, a member of our department
http://www.chem.harvard.edu/groups/walker/index.html
She told me about a *chemical reactivity* project that involves inhibitors
that her lab is exploring for a protein called OGT (If you search OGT in the
protein databank you get an idea).
They have ~35 modified inhibitors and docking calculations. What they want
to know is based on the quantum chemistry of the molecule alone, how
reactive is a C=0 moiety. If too reactive, it reacts with lysines across the
protein, if not that reactive, it doesn't react with the inhibitor at the
active site.
This probably would require calculating properties such as natural
bond-order analysis, electron localization function (?), Fukui orbitals, or
the like, to see if we can correlate reactivity with actual "descriptors"
that we have from quantum chemistry. The molecule size is ~4 heteroatom
rings, not that different from our screensaver molecules.
If anybody is interested in this task as a side project, let me know. Carlos
Amador is interested in helping from Mexico, but I think we need an
additional local person. The Walker group postdoc is a very enthusiastic
person. Some of these projects have been benefitial to some group memberes
(eg. Leslie or Dmitrij) but can take some time.
The point is that they think this is of high impact, if comp. chem. can help
correlate activity, as potentially we could help design a strong inhibitor
with electronic structure. This is the first inhibitor (that she knows of)
that reacts *twice* with the protein, effectively "zipping" the reactive
site. The protein is apparently quite important biologically and therefore
there is a candidate molecule they found that is already being marketed as a
drug, if I understood correctly.
Depending if there are people interested (or not) I will decide if we take
up this challenge. It would involve as you see, some tools that we have been
using for other projects, e.g. SERS or screensaver.
Best,
Alan
Alán Aspuru-Guzik | Associate Professor
Harvard University | Department of Chemistry and Chemical Biology
12 Oxford Street, Room M113 | Cambridge, MA 02138
(617)-384-8188 |
http://aspuru.chem.harvard.edu