AMBER Archive (2009)

Subject: RE: [AMBER] non standart residue library creation with tleap (Zn atom)

From: Ross Walker (ross_at_rosswalker.co.uk)
Date: Tue Nov 24 2009 - 10:28:21 CST

Hi Andrew,

You could take a look at my Ph.D. thesis here:

http://www.rosswalker.co.uk/reports1.htm

And also the following two publications:

Walker, R.C., Klug, D.R. et al. "Large and fast relaxations inside a
protein: Calculation and measurement of reorganisation energies in alcohol
dehydrogenase.", J. Phys. Chem. B., 2002, 106(46). 11658-11665

Walker, R.C., Cho, B.M., Amer, H., Mercer, I.P., Gould, I.R., Klug, D.R.,
"The effect of adiabaticity on electron dynamics in Zinc Myoglobin." J.
Phys. Chem. B., 2005, 109(12), 5954-5961.

You can get pdfs of these from here:

http://www.wmd-lab.org/publications.htm

I suggest reading these where I set up simulations for covalently bound zinc
atoms. I would also suggest reading the cited Ulf Ryde papers which include
discussions of parameter derivation for zinc.

What you are trying to do is way beyond the scope of what Antechamber and
the GAFF force field was designed to do, i.e. work with small ligands. In
your case you are in advanced territory and it is critical that you
understand what you are doing and how the different parameters etc flow
through the code. In my opinion you should calculate your charges manually,
you can look at how I did it in my Ph.D. thesis. Then you can build this
system yourself in Leap and also manually build yourself a frcmod using
parameters from Ryde or ones generated yourself. Trying to automate all of
this through antechamber will end up being more work in the long run for
questionable results.

Good luck,
Ross

> -----Original Message-----
> From: amber-bounces_at_ambermd.org [mailto:amber-bounces_at_ambermd.org] On
> Behalf Of Andrew Voronkov
> Sent: Monday, November 23, 2009 8:36 AM
> To: AMBER Mailing List
> Subject: Re: [AMBER] non standart residue library creation with tleap
> (Zn atom)
>
> This is kind of zinc finger and it is connected to four amino acids,
> not small molecule ligands. So in case of amino acids I should also
> define frcmod for this zinc atom and four amino acids which are bound
> to it? To construct frcmod file by antechamber or use the frcmod file
> which I've mentioned above?
> And the library in this case (saveoff zinc.lib) should also be defined
> for the zinc atoms and four amino acids to which it is connected,
> right?
>
> 23.11.09, 17:06, "FyD" <fyd_at_q4md-forcefieldtools.org>:
>
> > Andrew,
> >
> > You have two possibilities:
> >
> > - either you consider your Zinc atom not connected to your ligand
> and
> > you only need vdW paramaters for this Zinc atom (consequently, the
> > total charge of your Zinc = +2)
> > In this case, you DO use the files available @
> > http://q4md-forcefieldtools.org/Help/Andrew/
> >
> > - or you consider your Zinc atom connected to well-characterized
> > ligands and you will have to define bond, angle and dihedral FF
> > parameters as well (but the charge of the Zinc atom should not be =
> 2).
> > In this case, you canNOT use the files available @
> > http://q4md-forcefieldtools.org/Help/Andrew/
> > and you will have to define a FF library for "Zinc & its ligands"
> all
> > together.
> >
> > Does it help ?
> >
> > regards, Francois
> >
> >
> > > Where in this case I should get dihedrals and bond length, from my
> > > protein or this are some standarts?
> > >
> > > I've taken frcmod.zinc from this page:
> > > http://mayoresearch.mayo.edu/mayo/research/camdl/zinc_protein.cfm
> > >
> > > as far as in protein which I study zin is also tetrahedron
> > > coordinated then it should be ok. frcmod.zinc is below.
> > > The Zn parameters loads ok (I tried to replace Zn to Zn2 in
> > > frcmod.zinc, but no luck). I get the same for atom: .R 1311>.A
> Could not find type: ZN.
> > > Maybe this is still some PDB syntax problem or syntax with some
> > > atom-residues type in .off file against frcmod and(or) PDB?
> > >
> > >
> > > Amber Force Field Parameters for the Tetrahedron-Shaped Zinc
> Divalent Cation
> > > Loading library: ./ZN2.off
> > > Loading PDB file: ./2rf5-znparm.pdb
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > Added missing heavy atom: .R.A
> > > total atoms in file: 1665
> > > Leap added 1628 missing atoms according to residue templates:
> > > 12 Heavy
> > > 1616 H / lone pairs
> > >> saveamberparm MOL tnk.prmtop tnk.inpcrd
> > > Checking Unit.
> > > WARNING: There is a bond of 4.409856 angstroms between:
> > > ------- .R.A and .R.A
> > > WARNING: The unperturbed charge of the unit: 2.000000 is not zero.
> > >
> > > -- ignoring the warnings.
> > >
> > > Building topology.
> > > Building atom parameters.
> > > For atom: .R.A Could not find type: ZN
> > > Parameter file was not saved.
> > >>
> > >
> > >
> > >
> > > The frcmod file is below:
> > >
> > >
> > > Amber Force Field Parameters for the Tetrahedron-Shaped Zinc
> Divalent Cation
> > > MASS
> > > DZ 3.0
> > > Zn 53.380
> > >
> > > BOND
> > > DZ-Zn 640.0 0.90
> > > DZ-DZ 640.0 1.47
> > >
> > > ANGLE
> > > DZ-Zn-DZ 55.0 109.50
> > > DZ-DZ-DZ 55.0 60.0
> > > DZ-DZ-Zn 55.0 35.25
> > >
> > > DIHE
> > > Zn-DZ-DZ-DZ 1 0.0 35.3 2.00
> > > DZ-Zn-DZ-DZ 1 0.0 120.0 2.00
> > > DZ-DZ-DZ-DZ 1 0.0 70.5 2.00
> > >
> > > IMPROPER
> > >
> > > NONB
> > > DZ 0.000 0.00
> > > Zn 3.100 1.0E-6
> > >
> > >
> > >
> > > 23.11.09, 14:25, "FyD" :
> > >
> > >> Andrew,
> > >>
> > >> This frcmod file should only contains vdW parameters:
> > >> This takes 3 sec to do it by hands.
> > >> When you do all automatically, you do not understand what you
> do...
> > >> You just need to find these vdW parameters in the required
> paper:
> > >> See http://ambermd.org/Questions/mail/64.html
> > >>
> > >> See http://q4md-forcefieldtools.org/Help/Andrew/tleap.cmd
> > >> http://q4md-forcefieldtools.org/Help/Andrew/frcmod.zinc
> > >> replace xxxx yyyy by the Zinc vdW parameters...
> > >>
> > >> regards, Francois
> > >>
> > >>
> > >> > Hm, frcmod should be prepared by antechamber. Now we got
> antechamber
> > >> > error here:
> > >> >
> > >> > $ antechamber -i zn2.pdb -fi pdb -o zn2.prepin -fo prepi -c
> bcc -s 2
> > >> >
> > >> > Running: /amber10/bin/atomtype -i ANTECHAMBER_AC.AC0 -o
> > >> > ANTECHAMBER_AC.AC -p gaff
> > >> >
> > >> > Total number of electrons: 0; net charge: 0
> > >> >
> > >> > Running: /amber10/bin/mopac.sh
> > >> > Error: unable to find mopac charges in mopac.out
> > >> >
> > >> > This is zn2.pdb, maybe there is something wrong with PDB file:
> > >> >
> > >> > HETATM 1666 ZN ZN2 1 -34.053 -24.945 -27.759 1.00
> 27.33
> > >> > ZN
> > >> > END
> > >> >
> > >> >
> > >> >
> > >> > 20.11.09, 18:47, "FyD" :
> > >> >
> > >> >> Quoting Andrew Voronkov :
> > >> >>
> > >> >> > Ok, interesting. The "Unknown residue" message doesn't
> appear
> > >> >> > anymore while loading pdb...but I have now problem in
> saving amber
> > >> >> > params files:
> > >> >> >
> > >> >> > Building topology.
> > >> >> > Building atom parameters.
> > >> >> > For atom: .R.A Could not find type: ZN
> > >> >> > Parameter file was not saved.
> > >> >>
> > >> >> See updated http://q4md-
> forcefieldtools.org/Help/Andrew/tleap.cmd
> > >> >> & BTW do not forget to prepare a "frcmod" file for setting
> vdW
> > >> >> parameters for your Zinc atom, I forgot to add this step
> > >> >>
> > >> >> F.
> > >> >>
> > >> >>
> > >> >> > 20.11.09, 16:40, "FyD" :
> > >> >> >
> > >> >> >> Andrew,
> > >> >> >>
> > >> >> >> > Yes! It works now! The problem was that I've changed
> the
> > >> atom name
> > >> >> >> > rather than residue name in PDB and also residue name
> was also
> > >> >> >> > shifted a bit left and was at last stage not ZN2 but
> N2.
> > >> >> >>
> > >> >> >> ok. This is a classical problem of recognition between
> > >> your PDB & the
> > >> >> >> FF libraries you load in LEaP.
> > >> >> >>
> > >> >> >> > I also wonder if it's ok to setup charge Zn2+ to a
> metal
> > >> ion bound
> > >> >> >> > to four amino acids or I should set up it as part of
> the
> > >> >> protein then.
> > >> >> >>
> > >> >> >> Two approaches are possible:
> > >> >> >> - The 1st one you consider Zn2+ not physically connected
> to your
> > >> >> >> ligands & the total charge of the atom Zn is +2 (BTW do
> > >> not forget to
> > >> >> >> prepare a "frcmod" file for setting vdW parameters for
> > >> your Zinc atom,
> > >> >> >> I forgot to add this step @
> > >> >> >> http://q4md-forcefieldtools.org/Help/Andrew/tleap.cmd).
> > >> >> >> - The second one you derive charges for your Zn-complex
> > >> were you will
> > >> >> >> consider connections between Zinc & well-established
> > >> ligands. In this
> > >> >> >> case, the charge of Zn2+ should decreased to... some
> value ;-)
> > >> >> >> I suggest you to use R.E.D.-III.3 and/or R.E.D.
> Server/R.E.D.-IV in
> > >> >> >> the latter case.
> > >> >> >>
> > >> >> >> regards, Francois
> > >>
> > >>
> > >>
> > >> _______________________________________________
> > >> AMBER mailing list
> > >> AMBER_at_ambermd.org
> > >> http://lists.ambermd.org/mailman/listinfo/amber
> > >>
> > >>
> > >
> > > _______________________________________________
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> > >
> > >
> >
> >
> >
> > F.-Y. Dupradeau
> > ---
> > http://q4md-forcefieldtools.org/FyD/
> >
> >
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> >
>
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