Dear Robin, dear Ross,
> I am working on parameterizing NADH for an updated tutorial on RESP and
> Paramfit, but I'm running into problems with how to obtain an optimized
> structure. I downloaded an "ideal" solvated structure from the PDB and ran
> a B3LYP optimization in gas phase according to the procedure outlined in
> tutorial A1.
I do not think that:
- the tutorial A1 is a reference; this was discussed some time ago and
nothing was corrected so far. I even think that this tutorial teaches
wrong approaches to new users.
- using B3LYP will help in the case of NADH as this structure is
multiply charged.
- using a 'solvated' structure will help as NADH can also be docked in
a protein site (see Dean's answer as well in a previous email).
> The resulting structure is folded up and quite different from
> the more realistic solvated structure, so I was wondering how to proceed.
I think the "building block approach" is an answer to your question.
See first:
http://onlinelibrary.wiley.com/doi/10.1002/jcc.540161106/abstract
& for instance the nucleic acid case.
then:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918240/
Concerning NADH, see the project related to biochemical cofactors in
R.E.DD.B. which follows this "building block approach":
http://q4md-forcefieldtools.org/REDDB/projects/F-90/ for instance or F-91.
> Running a RESP on an unrealistic structure doesn't seem like it would give
> sensical results.
I agree
> Is there any sort of "industry standard" for approaching this problem? Ross
> Walker suggested conducting the optimization step using DFT with implicit
> solvent to perhaps obtain a better structure.
I do not think using implicit solvent conditions and/or DFT in the
geometry optimization step will help for multiply charged bio-organic
structures; My feeling is that you should go back to the "building
block approach" originally described by the Kollman's group in the
middle of the 90tees and developed nowadays at q4md-forcefieldtools.org.
If you have questions about this "building block approach" do not
hesitate to ask more questions; You should find many pieces of
information in the F-90 R.E.DD.B. project.
I hope this helps.
regards, Francois
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Received on Fri May 04 2012 - 02:00:03 PDT
