Re: [Apbs-users] counter-ions

[Vigneshwar R. <vms...@gm...>]

Dear Dr. Baker,

Thank you very much for the clarification. I understand that for very small
simulation boxes and for low enough ionic strengths, it results only in
neutralizing counterions. Nevertheless, as you point out, to mimic a
realistic system, one needs to account for salt concentrations. I will set
up the simulations accordingly and perform calculations accordingly.

Thank you very much again!

Sincerely,
Vignesh

On Thu, Sep 23, 2010 at 9:58 AM, Baker, Nathan <Nat...@pn...> wrote:

>  Hi Vignesh –
>
>
>
> I agree with your comment that ionic systems are macroscopically
> electroneutral and that molecular simulations should also be
> electroneutral.  However, I don’t agree with your comment that molecular
> dynamics simulations are only performed with neutralizing counterions.
> There are many counter-examples for this where investigators set up the
> system to approximate a bulk ionic strength.  For *very** small*simulation boxes, this may result in only neutralizing counterions.
> However, the presence of *only* neutralizing counterions hardly ever
> represents a realistic physical system – instead, it is generally just an
> artifact of simulation.
>
>
>
> I would urge you to specify salt concentrations for your system and add the
> appropriate number of counterions for that salt concentration rather than
> simply adding neutralizing ions.
>
>
>
> Good luck,
>
> __________________________________________________
> *Nathan Baker*
> Chief Scientist for Signature Science
> Pacific Northwest National Laboratory
>
>
>
> *From:* Vigneshwar Ramakrishnan [mailto:vms...@gm...]
> *Sent:* Tuesday, September 21, 2010 11:50 PM
>
> *To:* Baker, Nathan
> *Cc:* apb...@li...
> *Subject:* Re: [Apbs-users] counter-ions
>
>
>
> Dear Dr. Baker,
>
>
>
> May I try to understand why the system I described is not realistic:
>
>
>
> In a real system, the ions always come in pairs. That is they are a result
> of dissociation of salts (eg. NaCl --> Na+ and Cl- ). Hence, ideally, one
> should add (in MD simulations) both positive and negative ions - defining
> the ionic strength of the solution. However, in MD simulations, as far as I
> know, people only add appropriate number of neutralizing ions. The
> assumption, probably, is that these neutralizing ions come to the vicinity
> of the biomolecule from a "bulk" salt solution. Given that the molecular
> interaction parameters for ionic species are not accurate enough yet, this
> assumption avoids the potential artefacts that might be introduced because
> of larger number of ions in the MD simulations. Nevertheless, as you point
> out, this is also a bad way to model the electrostatics in the system.
>
>
>
> Am I right?
>
>
>
> In calculating the polar energy, APBS accounts for the "bulk" ionic
> strength. Hence it will have both the positive and negative charged
> species.
>
>
>
> Thank you,
>
> Sincerely,
>
> Vignesh
>
> On Wed, Sep 22, 2010 at 10:54 AM, Baker, Nathan <Nat...@pn...>
> wrote:
>
> Hi Vignesh –
>
>
>
> Unfortunately, the system you describe is not realistic and running a
> molecular simulation with only neutralizing counterions is almost always a
> bad way to model biomolecular electrostatics.  You could probably simulate
> this system in a Poisson-Boltzmann calculation by looking at the limit of a
> series of calculations as they tend to zero ionic strength; however, it
> might be better to reconsider the setup of your molecular simulation
> instead.
>
>
>
> Good luck,
>
> __________________________________________________
> *Nathan Baker*
> Chief Scientist for Signature Science
> Pacific Northwest National Laboratory
>
>
>
> *From:* Vigneshwar Ramakrishnan [mailto:vms...@gm...]
> *Sent:* Tuesday, September 21, 2010 7:46 PM
> *To:* Baker, Nathan
> *Cc:* apb...@li...
> *Subject:* Re: [Apbs-users] counter-ions
>
>
>
> Dear Dr. Baker,
>
>
>
> I am referring to the MD simulation system where only the neutralizing Na+
> ions and the protein-DNA complex are present.
>
>
>
> In the polar energy calculation, APBS requires that both the positive and
> negative mobile ions be at equal concentrations (electro-neutral). However,
> in the MD simulations, we do NOT have negative mobile ions. I am not able to
> understand how to reconcile this.
>
>
>
> Sincerely,
>
> Vignesh
>
>
>
> On Wed, Sep 22, 2010 at 10:38 AM, Baker, Nathan <Nat...@pn...>
> wrote:
>
> Hi Vignesh –
>
>
>
> I’m not sure what you mean by a system in which only Na+ ions exist.  Are
> you referring to an infinite dilution sodium-DNA complex where only a
> neutralizing number of Na+ ions are present?
>
>
>
> Thanks,
>
> __________________________________________________
> *Nathan Baker*
> Chief Scientist for Signature Science
> Pacific Northwest National Laboratory
>
>
>
> *From:* Vigneshwar Ramakrishnan [mailto:vms...@gm...]
> *Sent:* Tuesday, September 21, 2010 6:53 PM
> *To:* apb...@li...
> *Subject:* [Apbs-users] counter-ions
>
>
>
> Dear Users,
>
>
>
> I am trying to calculate the binding energy of protein-DNA complex using
> the MM/PBSA methodology. I have now a series of ensemble structures from
> molecular dynamics simulations for which I use APBS to calculate the apolar
> and polar energies. In the MD simulations, I had added 28 Na+ ions
> as counter-ions for electro-neutrality of the system. It does NOT contain
> any negatively charged ions.
>
>
>
> From a previous post in this forum, I understand that these counter-ions
> are assumed to come from a bulk system where the positive and negative ions
> coexist in equal concentrations (ie, in electro-neutrality). However, what I
> don't understand is that if one assumes that the negative ions also
> coexisted, the net result in the binding energy would be different from that
> which we would get if only the Na+ ions were present. If that is the case,
> then are we capturing the binding energies correctly from the MD
> simulations?
>
>
>
> Maybe I am missing something very simple. Can anybody shed some light on
> it?
>
>
>
> Thank you,
>
> Sincerely,
>
> Vignesh
>
>
> --
> R.Vigneshwar
> Graduate Student,
> Dept. of Chemical & Biomolecular Engg,
> National University of Singapore,
> Singapore
>
> "Strive for Excellence, Never be satisfied with the second Best!!"
>
> I arise in the morning torn between a desire to improve the world and a
> desire to enjoy the world. This makes it hard to plan the day. (E.B. White)
>
>
>
>
> --
> R.Vigneshwar
> Graduate Student,
> Dept. of Chemical & Biomolecular Engg,
> National University of Singapore,
> Singapore
>
> "Strive for Excellence, Never be satisfied with the second Best!!"
>
> I arise in the morning torn between a desire to improve the world and a
> desire to enjoy the world. This makes it hard to plan the day. (E.B. White)
>
>
>
>
> --
> R.Vigneshwar
> Graduate Student,
> Dept. of Chemical & Biomolecular Engg,
> National University of Singapore,
> Singapore
>
> "Strive for Excellence, Never be satisfied with the second Best!!"
>
> I arise in the morning torn between a desire to improve the world and a
> desire to enjoy the world. This makes it hard to plan the day. (E.B. White)
>



-- 
R.Vigneshwar
Graduate Student,
Dept. of Chemical & Biomolecular Engg,
National University of Singapore,
Singapore

"Strive for Excellence, Never be satisfied with the second Best!!"

I arise in the morning torn between a desire to improve the world and a
desire to enjoy the world. This makes it hard to plan the day. (E.B. White)