Re: [AMBER] MD_Box_size_and_counterions_counting_general_rule

From: Antonio Amber Carlesso <>
Date: Thu, 8 Nov 2018 10:43:16 +0100

Hi all again,

As usual thank you again for you very insightful reply!
very useful and I will go through the articles as soon as possible!

On Wed, Oct 31, 2018 at 3:06 PM Matias Machado <>

> Dear Antonio,
> It may be worth reading the following recent paper of Karplus:
> Valid molecular dynamics simulations of human hemoglobin require a
> surprisingly large box size
> eLife 2018 []
> In practice the box size is usually chosen to avoid seeing the same
> molecule through PBC images, so you are simulating a solute in diluted
> conditions without having crystal artifacts... however representing bulk
> water in a proper way may be important to correctly describe the
> hydrophobic/hydrophilic balance in some cases as shown by Karplus...
> In case of the ions... notice that counterions alone are supposed to not
> contribute to the ionic strength as they should be already screened by the
> solute's charges... so a system with just counterions is supposed to have a
> zero ionic strength... when you start adding so called coions (salt) then
> you should take into account the presence of counterions to fit the desired
> salt concentration
> I invite you to read the recent paper of Schmit on that issue:
> SLTCAP: A Simple Method for Calculating the Number of Ions Needed for MD
> Simulation. JCTC 2018 []
> Regarding solvent volume for estimating salt concentration... IMAO, if you
> are simulating a diluted condition (a typical in-vitro experiment as David
> said), then the volume of the protein should be negligible in comparison to
> water, but in a typical simulation box this condition is not generally the
> case (solute volume ~ solvent volume), so what I do is calculating the
> solvent volume from the number of water molecules in the box and assuming a
> density of ~1 g/mL at 27°C, instead of using the simulation box volume. In
> that way, water volume should better represent the water activity (i.e. the
> water available to do something)...
> If you pretend to represent an in-vivo condition, where crowding plays a
> role, then that's more challenging because the protein volume can't be
> neglected from the equation an everything becomes very odd... IMAO, I think
> there is still a gap between the microscopic and macroscopic description of
> concentration in leaving cells or crowded condition... I mean, what is the
> real meaning of concentration in such cases? what are experimentalists
> really measuring?
> Any way, ions are still a matter of debate and research in MD...
> Best,
> Matias
> ------------------------------------
> PhD.
> Researcher at Biomolecular Simulations Lab.
> Institut Pasteur de Montevideo | Uruguay
> []
> []
> ----- Mensaje original -----
> De: "David A Case" <>
> Para: "AMBER Mailing List" <>
> Enviados: Jueves, 25 de Octubre 2018 11:18:59
> Asunto: Re: [AMBER] MD_Box_size_and_counterions_counting_general_rule
> On Thu, Oct 25, 2018, Antonio Amber Carlesso wrote:
> >
> > Is there any general rule to follow regarding the size of the box
> compared
> > to the molecular object(s) investigated?
> Commonly, Amber users include enough solvent around a molecular that
> that there is at least 12-15 Å between any solute atom and the edge of
> the box. This is typically done using the solvateBox or solvateOct
> commands in tleap.
> This is a compromise between accuracy and speed. It can be worth
> experimenting with large box sizes to see what happens.
> >
> > In addition, counterions that should be added to reflect “physiologic
> > condition”..
> >
> > Is there any general rule when it is reasonable to substract the volume
> of
> > the solute from the overall volume and when the volume of the solute can
> be
> > neglected in the overall counterions calculations?
> There is no general rule here. Use of "physiologic conditions" might
> make sense if you are expecting to compare with studies in cells; for
> comparisons to in vitro work, of course, different salt conditions might
> be more appropriate.
> I generally like to prepare simulations such that the *molal*
> concentration of salt is the same as that reported for whatever
> experiment seems most relevant. This avoids all questions of the solute
> partial molar volume. But if the differences are important to you, you
> would really need to use multiple box sizes, and look at the effective
> concentrations of ions far from the solute in your simulation. This is
> occasionally done with highly charged solutes like nucleic acids, or in
> studies where the distribution of ions is being investigated. It is
> rarely done if properties of the solute are of greatest importance.
> ....dac
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Received on Thu Nov 08 2018 - 02:00:02 PST
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