AMBER Archive (2006)

Subject: Re: AMBER: Using modified NA bases

From: Qizhi Cui (qzcui_at_scripps.edu)
Date: Wed Oct 25 2006 - 10:51:32 CDT

Hi Seth,

I used the R.E.D. program to prepare mol2 files for modified bases. It
works well.

The key step to create a library file for modified nucleotide is to
re-calculate the atomic partial charges. You can follow the procedures
described in the following paper to get RESP charges: P. Cieplak, W.D.
Cornell, C. Bayly, P. A. Kollman, J. Comp. Chem. 16, 1357 (1995).

Basically, you need first build a modified nucleoside (with your modified
base), then run RESP calculation. If you use R.E.D. program, you may get
the corresponding mol2 file as well. You may find the mol2 file for DMP
(dimethylphosphate) from R.E.DD.B. Or you can do the same calculation for
DMP. Then you need combine the nucleoside and DMP using multi-molecule
RESP fitting with charge restraints to get the final partial charges for
the modified nucleotide.

Now you can use xleap to create .off file for the modified nucleotide. You
need manually remove extra atoms and re-type the partial charges based on
your previous calculations.

To construct a duplex with modified nucleotide, you can first construct a
normal duplex for a given sequence. You can use nucgen to create a PDB
file. Then, find the residue to be modified, delete all its base atoms and
change its residue name to your modified nucleotide name (e.g. DM, which
must be consistent with the name in the .off file). Finally, you use xleap
to load the modified PDB file and the leap program will automatically add
the missing base atoms based on your .off file for the modified
nucleotide.

Hope this helps.

Qizhi

> Quoting sethl_at_gatech.edu:
>
>> I would like to know the most common way to go about building nucleic
>> acid
>> complexes with custom/modified bases. Right now I have generated a
>> library of
>> prep files that contain my modified bases but then how would I go about
>> constructing a structure file for a helicoidal duplex using these bases?
>
> R.E.D. generates Tripos mol2 files which can be used instead of prep
> files in LEaP.
> LIB = loadmol2 yourfile.mol2
>
> You can find nucleotide fragments in R.E.DD.B. as examples. See for
> instance:
> Projects: F-61 up to F-64; F-57 up to F-59
>
> regards, Francois
>
>
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