Re: ions behavior in protein-water box:

From: Emanuelle Bachelet (
Date: Thu Oct 30 2008 - 14:38:13 CDT

Attraction between Ca2+ ion and Aspartic acid will have the potential of
inducing conformational changes in the protein locally. If that happens,
these local conformational changes might induce long range effects and I do
not see the relevance of long enough computational time as there's not just
one but 4 Ca ions. Even if one ion dissociates and leaves, another might
come and cause another conformational change.

I am interested in conformational changes in a protein among its isoforms.
If there are spurious conformational changes induced by ions in one
simulation and not the other, the results are meaningless imo to be compared
amongst each other to look for any differences in conformations of the three
isoforms which differ in sequence identity by little bit.

Imagine anyone doing a reaction path calculation: I might be wrong in my
judgement but ions leading to unrealistic conformational changes along the
path, the dynamics path calculation will no longer be valid.

May be then its best to use 9 Na+ ions to reduce the impact on protein
conformations being close to ions. I also see sodium ion is less mobile in
my simulations compared to Ca2+ ions - one reason might be due to less
coulombic attraction.


On Thu, Oct 30, 2008 at 2:50 PM, Christopher Gillespie <
> wrote:

> Ema,
> Given enough simulation time, and as Axel already mentioned the longer
> range coulombic effects, I would expect either Ca or Na to associate with
> Asp or Glu residues. The only other option is no ions, but PME really
> should have a neutral system.
> Chris
> On Oct 30, 2008, at 1:24 PM, Emanuelle Bachelet wrote:
> Actually, one the Ca ions comes close to an aspartic acid - this is so not
> good!
> Well, one simulation I am trying now is to just fix the ions around their
> equilibrated positions - (all these are more than 10A from any protein atom
> after I finished equilibration). I will monitor the progress and if it
> dosen't work I will introduce 9 sodium ions - I hope I won't have to make
> the water box bigger to accomodate all of them.
> I used Ca ions so I could keep the water box reasonable size and keep ions
> at large distance from each other (instead of having 9 sodium ions since I
> deleted the waters manually and put the ions in place of those 5 water
> molecules). But i didn't think earlier that the Ca2+ will have such dramatic
> effects.
> Many thanks,
> Ema.
> On Wed, Oct 29, 2008 at 6:39 PM, Axel Kohlmeyer <
>> wrote:
>> On Wed, 29 Oct 2008, Christopher Gillespie wrote:
>> CG> Ema,
>> CG>
>> CG> I agree that the ions shouldn't effect the protein dramatically, but
>> if you
>> CG> are concerned with the interactions of the ions with the protein why
>> include
>> CG> the Ca2+ and not just Na+? If the protein is not restrained in any
>> way the
>> CG> ion effect over the length of the simulation should not be too
>> dramatic.
>> CG> Simple Brownian motion is going to move the ions with or without the
>> CG> protein.
>> to add to this: if you put a -9 charged object somewhere,
>> it _is_ highly attactive to objects of the opposite charge,
>> and doubly so for calciums. ;-)
>> coulomb interactions are quite strong and range far, so
>> i would not be too surprised to have some cations sticking
>> rather closely to your protein. do you know for sure that
>> there are none? how deeply are the anionic components buried?
>> cheers,
>> axel.
>> CG>
>> CG> Best,
>> CG> Chris
>> CG>
>> CG>
>> CG> On Oct 29, 2008, at 5:56 PM, Emanuelle Bachelet wrote:
>> CG>
>> CG> >Hi Chris,
>> CG> >
>> CG> >By closer I mean less than 5A, I haven't measured the exact distance
>> CG> >because it's fluctuating. But imo, less than 5A means ions are going
>> to
>> CG> >modify the electrostatic interactions with/on the protein. Ions
>> should be
>> CG> >just to neutralize the system not to interact with the protein.
>> CG> >
>> CG> >I will also have a look at the reference you mention.
>> CG> >
>> CG> >Thanks,
>> CG> >Ema
>> CG> >
>> CG> >On Wed, Oct 29, 2008 at 4:05 PM, Christopher Gillespie
>> CG> ><> wrote:
>> CG> >Ema,
>> CG> >
>> CG> >What exactly do you mean by "closer"? Ion association with protein
>> CG> >surfaces is not necessarily an "incorrect" observation rather ions
>> can
>> CG> >interact with various parts routinely. Take a look at the work of
>> Pavel
>> CG> >Jungwirth on ion protein association.
>> CG> >
>> CG> >Best
>> CG> >
>> CG> >Chris
>> CG> >
>> CG> >
>> CG> >
>> CG> >On Oct 29, 2008, at 2:44 PM, Emanuelle Bachelet wrote:
>> CG> >
>> CG> >Hello,
>> CG> >
>> CG> >I have a question regarding ions in a simulation.
>> CG> >
>> CG> >I have a protein that has a net charge of -9 (it includes one of the
>> CG> >residues which is phosphorylated). I immersed this protein in water
>> box it
>> CG> >and added 4 calcium ions and one sodium ion to neutralize the overall
>> CG> >charge.
>> CG> >
>> CG> >But when my simulation system reaches .5ns of production dynamics
>> (NVE),
>> CG> >some ions move closer to the protein. In my opinion, they should not
>> come
>> CG> >too close to protein so as to modify the protein behavior. Does this
>> mean
>> CG> >that I constrain the ions at a particular position?
>> CG> >
>> CG> >thanks,
>> CG> >Ema.
>> CG> >
>> CG> >
>> CG>
>> CG>
>> --
>> =======================================================================
>> Axel Kohlmeyer
>> Center for Molecular Modeling -- University of Pennsylvania
>> Department of Chemistry, 231 S.34th Street, Philadelphia, PA 19104-6323
>> tel: 1-215-898-1582, fax: 1-215-573-6233, office-tel: 1-215-898-5425
>> =======================================================================
>> If you make something idiot-proof, the universe creates a better idiot.

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