AMBER Archive (2006)

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

From: Jiri Sponer (sponer_at_ncbr.chemi.muni.cz)
Date: Sun Nov 05 2006 - 16:01:27 CST

Besides that, I would suggest to use good QM
to check the behavior of key torsional profiles.
If a large discrepancy exists then the force field should
likely be adjusted. We did not work on NA-drugs for a while,
but appears to me that most authors tend to get their
drug force fields as fast as possible, while many
of these molecules are horribly complex.

Best wishes, Jiri

-------------------------------------------------------
Jiri Sponer
Institute of Biophysics
Academy of Sciences of the Czech Republic
Kralovopolska 135
CZ-61265 Brno
Czech Republic
e-mail: sponer_at_ncbr.chemi.muni.cz
fax: 420 5412 12179
phone: 420 5415 17133
http://www.ibp.cz/labs/LSDNA/
-----------------------------------------------------------

[ Charset ISO-8859-1 unsupported, converting... ]
> 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?
> >
> >
> >
> > Erweitern Sie FreeMail zu einem noch leistungsst?rkeren E-Mail-Postfach!
> > Mehr Infos unter *http://freemail.web.de/home/landingpad/?mc=021131*
> > [http://freemail.web.de/home/landingpad/?mc=021131]
>
> 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
>
>
> -----------------------------------------------------------------------
> The AMBER Mail Reflector
> To post, send mail to amber_at_scripps.edu
> To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu
>
-----------------------------------------------------------------------
The AMBER Mail Reflector
To post, send mail to amber_at_scripps.edu
To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu