Re: AMBER: simulation with Mg2+ ions and counter ions

From: Lihua Wang <lhw.broyde.nyu.edu>
Date: Sat, 9 Jul 2005 04:11:42 -0400 (EDT)

Hi according to our experience, if some negatively charged atom is close
enough to Mg2+ (for example, the Mg2+ ions in polymerases or in kinases
and the COO- group of the nearby amino acid residues), this distance is
unlikely to change greatly during simulation. By close enough, I mean
<=2.8 angstroms. By "unlikely to change greatly", i mean you will unlikely
see the distance go beyond 3 angstroms. there are several reasons i could
think of:

1. the interaction between the Mg2+ and your Cl- is very strong and there
is a limited number of solvent molecules nearby to penetrate.

2. most likely you assigned a partial charge of +2 to the Mg2+ and -1 to
the Cl-. This does not necessarily reflects the real situation. There have
been reports that charge associated with Mg ions is "dampened" by the
solvent to something like 1.4 instead of 2.0. Using charge = +2 for Mg
might account for the unexpected stability of interactions between Mg and
negatively charged atoms/ions. However, there is probably no easy way
to use a non-integer charge value for ions. We have thought about
associating Mg2+ with a neighboring residue/entity and treat them as ONE
customized (non-standard) residue and compute the RESP charges. This will
likely "soften" the charge on Mg a bit.

3. The added Cl- ion might be too "artificial". i.e. usually Mg2+ at
binding site plays some critical roles in stablizing the bound ligand. I
am not sure how "physiological" it is to have this Cl- so close to the
Mg2+ and what kind of impact it will have on the binding interactions.
This has to be considered carefully...It is probably safer to add a couple
water molecules around Mg2+ first (thus Cl- cannot be that close to Mg2+)
and then neutralize your system by adding Cl-. Adding water is
likely "softer" than adding Cl- directly.

just my 2 cents.

Lihua

On Sat, 9 Jul 2005, Ye Mei wrote:

> Date: Sat, 9 Jul 2005 14:54:16 +0800
> From: Ye Mei <ymei.itcc.nju.edu.cn>
> Reply-To: amber.scripps.edu
> To: amber mailing list <amber.scripps.edu>
> Subject: AMBER: simulation with Mg2+ ions and counter ions
>
> Dear Amber users
>
> Please help to check whether my simulation is reasonable.
> I am trying to study a certain ligand binding to a protein with Mg2+ ions. First, I docked this ligand to the binding site using autodock. In the docking procedure, I included neither the Mg2+ ion, counter ions nor the water molecules near the binding site. Then I took some binding modes and add Mg2+ to the protein and locate it where it was in the pdb file. 2 CL- ions were then added to this complex to neutralize the whole system. One of the CL- ion is binded to this Mg2+ ion with distance less than 3A. Periodic water box is added to this complex with 8 A between the protein and the unit boundary. Minimization and 2ns MD simulation under 300K were applied to this system. But I found that the CL- ion that is bonded to Mg2+ has not been pushed away by water molecules, but is still there. I guess maybe the simulation time is not long enough, though the whole system has seemed to in equilibrium for a very long time. But my computer resource is very limited, and I cannot give an!
> ot!
> her ns simulation for each binding mode.
> So, can I just stop here, and calculate the binding free energy? If not proper, is there any easy way for me to correct it?
>       
>
> Best regards,
>
> Ye Mei
> ymei.itcc.nju.edu.cn
> Institute of Theoretical and Computational Chemistry
> Key Laboratory of Mesoscopic Chemistry
> School of Chemistry and Chemical Engineering
> Nanjing University
> Nanjing 210093
> P.R.China
> 2005-07-09
>
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Received on Sat Jul 09 2005 - 09:53:01 PDT
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