AMBER Archive (2004)

Subject: Re: AMBER: Pang-model of Zn2+

From: Peter Oelschlaeger (poe_at_caltech.edu)
Date: Thu Mar 25 2004 - 19:44:01 CST

Dear Oliver,

I have had very good experiences with the "Pang-model". I used it for a
binuclear metallo-beta-lactamase (Protein Eng. 2003 May;16(5):341-50 and
Biochemistry. 2003 Aug 5;42(30):8945-56).
It always depends on what you want: if you just want a stable zinc
binding site, you will be happy with a bonded approach like Ken Merz'
group uses it. In our case, we explicitely wanted to look at dynamics
and sensitivy of the active site and allow breakdown of the zinc-ligand
interactions. Therefore the Pang-model is ideal in MD simulations.
About the fusion of your hydroxide ion to the dummy ion: I thought that
was ruled out by the van der Waals radius of the central zinc atom which
extends beyond the dummy atom radii (r = 3.1 Å, e = 1E-6 kcal/mol).
Maybe you should check on that. In general, we always constrain the
zinc-dummy molecules during minimization and heating and then gradually
release the constraints at the simulation temperature. In your case it
might make sense to do that for the hydroxide, as well.
Hope this helps. Let me know if I can be of further assistance.

Best regards,

Peter

Oliver Hucke wrote:

> Dear All,
>
> I am wondering if people out there have experience with the Pang
> approach to modeling Zn2+ in proteins?
>
> I am using the tetrahedral divalent cation approach of Pang, i.e. the
> 2 positive charges are distributed on 4 dummy atoms at the apices of a
> tetrahedron around the Zn. (Prot. Science, v9, pp. 1857)
> One of the ligands of the zinc is a hydroxyl ion. During the
> minimization of my system this ion fuses with one of the dummy atoms,
> which leads to infinite electrostatic energy.
>
> The fusion seems to happen because the dummy atom has no repulsive van
> der Waals properties (r=0) while its distance to the zinc is flexible
> (force constant = 540). It moves from its equilibrium distance from
> the Zn (0.9A) to a distance close to the r-value of the oxygen (1.7A).
> This comes with a penalty in bond energy dummy-zinc but the
> electrostatics overcome this barrier.
>
> Has anybody encountered similar problems with this Zn2+ model?
> What is the reasonable behind a flexible zinc dummy distance? Would it
> not be better to fix this distance?
>
> Best regards,
> Oliver
> 

-- 
**************************************************
Peter Oelschlaeger, Ph.D.
Mayo lab, Division of Biology, Caltech
1200 E. California Blvd., mail code 114-96
Pasadena, CA 91125-9600

Phone: 	(626) 395-8085, Lab: (626) 395-6407
Fax:	(626) 440-7231
Email:	poe_at_caltech.edu
http://www.mayo.caltech.edu
**************************************************

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