From: Baker, N. <Nat...@pn...> - 2010-09-23 13:31:11
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Hi Xevi - Short answer: No. Long answer: The most common formulation of the PB equation is based on a grand canonical ensemble that effectively places the system in equilibrium with a salt solution bath of the desired concentration. The net result is that, for sufficiently large boxes, the bath contributes the necessary number of counterions to allow the system to reach approximate neutrality. In any case, adding explicit counterions would be difficult since their positions would not likely be fixed and therefore would require some other type of sampling. __________________________________________________ Nathan Baker Chief Scientist for Signature Science Pacific Northwest National Laboratory From: Xevi Biarnés (SISSA) [mailto:xbi...@si...] Sent: Thursday, September 23, 2010 5:39 AM To: Vigneshwar Ramakrishnan Cc: Baker, Nathan; apbs-users Subject: Re: [Apbs-users] counter-ions I will take advantage of this thread to ask for some clarification in one point: when performing an implicit solvent calculation, such as in PB approximation, should the protein be also neutralized with "fixed" counter-ions? or the charge of the whole system has no effect in the calculation of energy and forces? thank you. Xevi. On Thu, Sep 23, 2010 at 7:18 AM, Vigneshwar Ramakrishnan <vms...@gm...<mailto:vms...@gm...>> wrote: 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...<mailto: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...<mailto:vms...@gm...>] Sent: Tuesday, September 21, 2010 11:50 PM To: Baker, Nathan Cc: apb...@li...<mailto: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...<mailto: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...<mailto:vms...@gm...>] Sent: Tuesday, September 21, 2010 7:46 PM To: Baker, Nathan Cc: apb...@li...<mailto: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...<mailto: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...<mailto:vms...@gm...>] Sent: Tuesday, September 21, 2010 6:53 PM To: apb...@li...<mailto: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. 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