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> Dear all,
>
> I am simulating DNA duplexes with intercalating hydrophobic, charged small molecules/dyes. I wonder which of the force fields is considered to be the best to date to provide the most reliable conformations for a DNA duplex? I am particularly interested in the conformations of the sugars.
>
> I have this question because I have performed a couple of 10ns runs with ff99 and ff10 parameters of just DNA duplex of 16 bp long to examine the performance of the force fields. The setup of the test runs is very simple, unrestrained MD in NTP ensemble, explicit solvent (TIP3P), neutralized system with Na+.
>
> Both ff sets performed reasonably good, the average structures do still look like B-form DNAs. Though, I have noticed some problems with the performance. When ff99is used the DNA becomes extended with time, the problem that was corrected in ff10. On the other hand, the ff10 force fields set provides smaller rise (bp to bp distance) of 2.8?, while the ff99 gives the expected value of 3.36?. ff99 also introduces bp inclination after some time, which is not the case with ff10. However, neither ff99 nor ff10 provides reasonable sugar puckers values... Though the ff99 set gives much more stable values for the sugar pucker then ff10, which just covers all possible conformations. This is just DNA, and when I introduce any of my dyes, the values for sugars are all over the conformation space with both ff sets.
>
> The knowledge about the sugar conformations is crucial for me, since from the experimental data the transition to A-form DNA is suspected, and it would have been nice to observe it with the MD. There is no crystal/nmr structures to use as a starting/reference point. So any ideas/suggestions would be very appreciated!
>
> Best regards,
> Anna
>
> -----------
> Anna Reymer,
> Physical Chemistry,
> Department of Chemical and Biological Engineering
> Chalmers University of Technology
> Kemiv?gen 10
> SE-412 96 Gothenburg
> Sweden
Dear Anna,
just short comment (I am momentarily out of lab so
cannot in detail scrutinize).
Sugar pucker is indeed difficult and force fields
are not perfect in this respect. There have been several
attempt to tune the chi/pucker but perfect solution
is not available and may even be impossible within
the basic force field approximation.
Nevertheless, the bsc0 works reasonably.
It depends on what accuracy do you need.
I do not suggest to use parm99 as it would sonner
or later accumulate a/g pathology.
About vertical separation or rise,
be careful, it is highly dependent on the
mathematics used.
Vertical separation or
rise (defined in that physical chemistry sense as "stacking
distance" in the local coordination frame)
is always relaxed for a given combination of the
other geometry parameters, i.e., it is a dependent parameter.
So just value of rise does not tell much.
The main problem in your project will definitely be
building up the structure of the DNA/ligand complexes.
Unless you have high-resoltion X-ray start, you
do not have much chance to create the right
starting structure.
The force field then desperately struggles with the
high-energy unrelaxed starting structure.
Best wishes, Jiri
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Received on Thu Jun 02 2011 - 09:30:03 PDT
