Hi Robin,
Being a charged molecule (I assume you are charging the phosphates), and
having several possibilities of intramolecular hydrogen bonding, it would
be expected that the in vacuo structure fold upon itself due to
electrostatic attractions
in a way that would not be considered a "minimized" structure in aqueous
solution.
For nicotinamide cofactors, there is no "correct" structure... especially
at the nicotinamide ring, since different enzymes uniquely bind the syn
or anti orientation of the nicotinamide ring w/r/t the ribose via
rotation at the N-glycosidic linkage.
A piece-wise approach is the only way... I can't even imagine trying to
parameterize
the entire NADH structure simultaneously, and it's really not necessary
since most
of the structure is analogous to ATP (except for the pyrophosphate). The
hardest part is the parameterization of
a capped, reduced, nicotinamide ring because the non-planar nature of the
ring
causes all the ring dihedrals to be highly correlated. The next task would
be the
fine-tuning of the N-glycosidic dihedral to nicotinamide, analogously to
what was done recently for
the bases in RNA.
I have been writing paramfit tutorials for my students as well.
We should coordinate our efforts.
Dean
Dr. Dean Cuebas, Associate Professor of Chemistry
deancuebas.missouristate.edu, Ph 417-836-8567 FAX 417-836-5507
Dept. of Chemistry, Missouri State University
Springfield, Missouri 65897
On 5/2/12 5:44 PM, "Robin Betz" <rbetz.ucsd.edu> wrote:
>Hi all,
>
>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. The resulting structure is folded up and quite different from
>the more realistic solvated structure, so I was wondering how to proceed.
>Running a RESP on an unrealistic structure doesn't seem like it would give
>sensical results.
>
>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.
>
>Thanks,
>
>Robin Betz
>UC San Diego
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Received on Thu May 03 2012 - 09:30:04 PDT
