AMBER Archive (2009)

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

From: Andrew Voronkov (drugdesign_at_yandex.ru)
Date: Tue Nov 24 2009 - 02:40:42 CST

Actually my situation is very similar to described in this tutorial:
http://www.rosswalker.co.uk/tutorials/amber_workshop/Tutorial_four/
there is no RESP calculations there. So points 1-2 are a bit different there. Main point for me is the 3rd one. Why can't I just take dihedral angles and bond length parameters from the PDB file of the protein? It's the x-ray structure and zinc is far from ligand's binding site so taking parameters directly from PDB file can work then? I can actually try to use cap and not include zinc at all, but I expect some conformational changes there upon small ligand binding and second I just want to go through this zinc parametrization:)

PS points 1-2 with usage of your server will also take significant computational time as I understand.

23.11.09, 20:50, "FyD" :

> Dear Andrew,
>
> Now, we know that you want to model a Zinc amino-acid complex with
> atom connectivities between this Zinc atom and the considered amino
> acids.
>
> Let's proceed by order: you could try the following plan:
>
> 1) First, do you have the charges of this complex ?
> if no, I suggest you to use R.E.D. and/or R.E.D. Server to derive RESP
> or ESP charges embedded in a force field library (.mol2 file). Here,
> you have to optimize and get the MEP by QM, and then fit the RESP or
> ESP charges to the MEP.
> See http://q4md-forcefieldtools.org/RED/
> & http://q4md-forcefieldtools.org/Tutorial/
> Three difficulties here:
> ? Define the atoms of this complex and the corresponding fragment to
> be inserted in your protein
> ? Select the right theoretical level for the QM steps
> ? the fitting step might fail
> => This step is time consuming and requires some experience (or you
> take Mulliken charges after charge equivalencing for chemically
> equivalent atoms).
>
> 2) Define the FF atom types for your complex:
> Using Cornell et al. J. Am. Chem. Soc. 1995, 117, 5179 - Table 1, add
> the FF atom types in the FF library obtained in step 1)
> For this step, use a LEaP script and the "set" command. See examples
> in R.E.DD.B. I already provided you.
> See http://q4md-forcefieldtools.org/REDDB/projects/W-46/
> http://q4md-forcefieldtools.org/REDDB/projects/W-46/script1.ff
>
> 3) Manually create the "frcmod" file for missing FF parameters:
> "source leaprc.ff99SB" & run LEaP without this "frcmod" file, try to
> save the prmtop/prmcrd files: LEaP will fail, but will report the
> missing FF parameters. You manually create your frcmod file using the
> listing of missing FF parameters reported by LEaP.
> => This step is time consuming and requires some experience in force
> field parameter development (and try to get FF parameters from
> literature).
>
> You have all to generate your prmtop/prmcrd files.
>
> I tried to make the plan as short as possible - steps 1-3 represent
> loooot of work.
>
> regards, Francois
>
>
>
> Quoting Andrew Voronkov :
>
> > How to create frcomd file then? Manually?
> > http://www.rosswalker.co.uk/tutorials/amber_workshop/Tutorial_four/section4.htm
> > - how was this frcmod file created? Where should I get bond and
> > dihedrals parameters then, to measure them in the protein or to make
> > estimation by some software?
> > I don't quite understand how Ross Walker has made that frcmod file.
> >
> > 23.11.09, 18:31, "FyD" :
> >
> >> Quoting Andrew Voronkov :
> >>
> >> > 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?
> >>
> >> If you want to consider the whole complex i.e. Zinc-connected to
> >> amino-acids, you canNOT use what is available @
> >> http://q4md-forcefieldtools.org/Help/Andrew/
> >>
> >> You need to create a frcmod file + an off FF library for your Zn-amino
> >> acid complex.
> >>
> >> my mistake:
> >> I do NOT think Antechamber handles metal atoms.
> >>
> >> regards, Francois
>
>
>
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