Re: ions behavior in protein-water box:

From: Emanuelle Bachelet (
Date: Fri Oct 31 2008 - 12:08:53 CDT

I ran a simulation of 0.6ns anyways with ions constant to see if there are
any clatharate formation etc and any subsequent effect on protein. For those
of you who want to know what happens if I keep ions are kept constant in
protein-water simulation.

The left panel of the figure attached is 0ns (with red color water which
surrounded ions at 0ns). The right panel of the figure attached is 0.6ns
(with yellow water which surrounded ions at 0.6ns). You can see these waters
are not static or forming any clatharates at any point in time in the

I am not arguing which behavior is correct:
I was just curious as to what happens if the ions are more than 15 angstrom
away from the protein and are held fixed and only interested in keeping the
system neutral for PME. The effect of ions on protein conformation is still
at its infancy it seems and it's hard for someone to rerun a simulation with
limited resources if the ion ends up entering the catalytic active site of a
protein at 10 or 15ns.


On Thu, Oct 30, 2008 at 6:02 PM, Leandro Martínez <> wrote:

> Dear Ema,
> The cellular environment contains a lot of ions, that usually will
> interact with the negatively charged amino acids of the surface
> of proteins. These interactions are dynamic, in the sense
> that the ions generally stay some time near these side chains, then
> leave, than another ion comes, etc. A realistic simulation
> should include ions according to the ionic content of the actual
> physiological environment (although doing this can be much
> more complicated than one might think). Therefore, the presence
> of ions near the surface of your protein can be very important,
> even for the stabilization of the protein structure. You could
> get spurious results as well by not including some ions in
> your simulations.
> Anyway, different proteins react differently to these variables.
> If you think that this can be crucial for the properties you are
> studying, you should perhaps study the effect of the ionic
> content in your simulation separately.
> At the same time, you should avoid taking conclusions about
> the mobility of the ions by visually inspecting small trajectories.
> There are other measures that provide more quantitative results,
> as the diffusion coefficient.
> For example, in general, sodium ions will move more than
> calcium ions, both because they are less charged and because
> their mass is smaller.
> Better than studying ion mobility, on the other side, try studying the
> stability of the protein structure near these charged side chains
> in the presence or absence of these counterions.
> Leandro.
> On Thu, Oct 30, 2008 at 5:38 PM, Emanuelle Bachelet <
>> wrote:
>> Hey:
>> 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.
>> Thanks,
>> Ema.
>> 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------=_Part_25238_31443095.1225472933771--

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