AMBER Archive (2006)

Subject: Re: AMBER: Combine amber-force field and gaff94 for one molecule?

From: M. L. Dodson (mldodson_at_houston.rr.com)
Date: Sun Nov 05 2006 - 13:35:34 CST

On Sunday 05 November 2006 11:45, Michel Becker wrote:
> Dear AMBER users
>
> I would like to perform a MD with a covalently bound DNA-drug complex.
> amber 7 and 8 is available.
>
> For the DNA I will use the AMBER force field but I would like to employ
> simultaneously the gaff force field for the drug.
>
> Therefore, one bond, four angles and a few dihedral angles at the
> connection between both residues will exhibit amber atom types as well as
> gaff atom types.
>
> Does any complications result from that circumstance?
>
>
>
> Best regards
>
> Michel Beacker?
>
>
>
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Here is the way I do this kind of simulation. I am assuming that
the drug is bound covalently to a base. You will have to remove
atoms from the normal base and the drug at the sites of the
drug-base bond so that valence of all species can be satisfied.
Create a new residue definition for a nucleotide from the cognate
normal nucleotide, but without the atom removed at the site of the
covalent bond. The sum of charges will not be zero. Create a new
residue definition for your drug, but when you come to the resp
charge fitting step, fix the charge of the atom removed (to
satisfy valences) from the drug to be zero and the charge for the
rest of the drug to equal the charge of the atom you removed from
the base. Edit the new drug residue definition to remove the atom
at the drug site bonded to the base. The sum of charges will not
be zero. However, after you combine things in LEaP, you will have
a charge neutral system. Use the 'bond' command in LEaP to form
the covalent bond between the drug and the base before you write
the prmtop file. This is done in exactly the same way you create
a disulfide bond in a protein.

This procedure assumes no change in charge distribution of the
base between the normal DNA nucleoside and that in the adducted
DNA. This is certainly not correct in detail, but probably is a
reasonable approximation for many kinds of studies. If you do not
want to make that assumption, you must create a new residue from
the drug PLUS the adducted base already bonded. This will mean a
much larger QM calculation to get the charges, and will involve
many more degrees of freedom for the conformation of the new
residue, probably necessitating a multi conformational resp charge
fit. I suggest you use RED if you want to do things this way.
(Actually I would use RED, with or without antechamber, for both
approaches). See the list archives for the URLs and discussions
of new residue definition. 

-- 
M. L. Dodson
Email:	mldodson-at-houston-dot-rr-dot-com
Phone:	eight_three_two-56_three-386_one

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