Re: [AMBER] adding Na, K and Cl ions matching intracellular conc

From: Matias Machado <mmachado.pasteur.edu.uy>
Date: Fri, 06 Mar 2020 12:32:57 -0300 (UYT)

just a correction: "As we proved for SLTCAP,..." => "As we proved for SPLIT,..."

:-P

Matias

----- Mensaje original -----
De: "Matias Machado" <mmachado.pasteur.edu.uy>
Para: "AMBER Mailing List" <amber.ambermd.org>
Enviados: Viernes, 6 de Marzo 2020 12:29:54
Asunto: Re: [AMBER] adding Na, K and Cl ions matching intracellular conc

Dear Vaibhav,

Dealing with polyvalent salts (e.g. CaCl2) and complex mixtures is not a trivial issue...

The "rule" of just dividing by N is wrong as the charge of each ionic specie must be considered to preserve the electroneutrality of the system.

For that, Salinator utility of CHARMM-GUI uses a more general expression of SPLIT:

  N+ = No - Q/(2*Z+)
  N- = Z+*No + Q/2

where Z+ is the charge of the cation, see [http://www.charmm-gui.org/?doc=input/solution][https://doi.org/10.1002/jcc.20945].

But be aware that its application range wasn't validated, as we did in SPLIT. Indeed, the following authors' recommendation may be wrong:

"In the case that the number of an ion type becomes negative due to highly charged biomolecular systems such as DNA or RNA, Solvator displays a warning and asks users to increase the concentration." [https://doi.org/10.1002/jcc.20945].

As we proved for SLTCAP, there is a clear cutoff (No/Q<1) at which deviations from SLTCAP are unacceptable (i.e the linearized Poisson‐Boltzmann assumption is not valid in that range). A similar rule should be set for the general expression.

Notice that former approximations are for one ion pair in the solution... to deal with complex salt mixtures (NaCl + KCl + CaCl2 + ...) you have to take into account the ionic strength of the solution... so adding (let say) 4 Ca2+ ions is different than adding 8 Na+ ions, despite the net charge is the same...

At the moment I don't know of any simple and general rule to tackle all these issues at the same time...

Alternative, you could try using a semigrand canonical osmostat [https://doi.org/10.1021/acs.jpcb.7b11734]. Despite being more accurate, in my experience it may be ~30 times slower than a regular NVT/NPT simulation.

Hope this helps...

Best,

Matias

----- Mensaje original -----
De: "Vaibhav Dixit" <vaibhavadixit.gmail.com>
Para: "AMBER Mailing List" <amber.ambermd.org>
Enviados: Jueves, 5 de Marzo 2020 1:19:41
Asunto: Re: [AMBER] adding Na, K and Cl ions matching intracellular conc

Dear Matias and Amber list,
Thanks for the interesting suggestions and reference (I'll read it in
detail soon).
Just wondering if one can generalize this to dividing the charge by n,
where n is the total number of unique ions.
E.g. divide by 3 in case we want a combination of NaCl (2.5 mM) and KCl
(140 mM) at their typical intracellular concentrations.
Using this one can then simulate situations where intracellular Ca ions
increases 10-1000 fold (here we will divide by 5 to account for NaCl, KCl
and CaCl2).

Please let me know your thoughts and if this approach is meaningful.
Thank you.

On Thu, Mar 5, 2020 at 5:55 AM Matias Machado <mmachado.pasteur.edu.uy>
wrote:

> you can also check this previous post:
>
> [http://archive.ambermd.org/202002/0194.html]
>
> Best,
>
> Matias
>
> ----- Mensaje original -----
> De: "Matias Machado" <mmachado.pasteur.edu.uy>
> Para: "AMBER Mailing List" <amber.ambermd.org>
> Enviados: Miércoles, 4 de Marzo 2020 21:23:01
> Asunto: Re: [AMBER] adding Na, K and Cl ions matching intracellular conc
>
> Dear Vaibhav,
>
> I recommend you to use the SPLIT method, which is described here:
>
> Split the Charge Difference in Two! A Rule of Thumb for Adding Proper
> Amounts of Ions in MD Simulations
> [https://doi.org/10.1021/acs.jctc.9b00953]
>
> The keyword "saltcon" has nothing to do in explicit solvent MDs.
>
> Best regards,
>
> Matias Machado
>
> ------------------------------------
> PhD.
> Researcher at Biomolecular Simulations Lab.
> Institut Pasteur de Montevideo | Uruguay
> [http://pasteur.uy/en/labs/biomolecular-simulations-laboratory]
> [http://www.sirahff.com]
>
> ----- Mensaje original -----
> De: "Vaibhav Dixit" <vaibhavadixit.gmail.com>
> Para: "AMBER Mailing List" <amber.ambermd.org>
> Enviados: Miércoles, 4 de Marzo 2020 9:49:40
> Asunto: [AMBER] adding Na, K and Cl ions matching intracellular conc
>
> Dear All,
> I'm interested in understanding if/which Na, K and Cl ions explicitly enter
> into the active site of a given protein during MD simulation.
> But I can't find a way/trick (from the manual or older posts) to add all
> these ions matching the intracellular concentrations and while keeping the
> system neutral.
> I'm guessing someone in the list must have already done a similar thing.
> Thus can someone please suggest me on this aspect.
> I'm assuming that if this can be done then I'll have to use saltcon=0 to
> avoid GB modelling for salt concentrations.
> Looking forward to receiving valuable suggestions from the list.
>
> Thank you and best regards.
> Vaibhav
>
>
> --
>
> Regards,
>
> Dr. Vaibhav A. Dixit,
>
> Visiting Scientist at the Manchester Institute of Biotechnology (MIB), The
> University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
> AND
> Assistant Professor,
> Department of Pharmacy,
> ▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄
> Birla Institute of Technology and Sciences Pilani (BITS-Pilani),
> VidyaVihar Campus, street number 41, Pilani, Rajasthan 333031.
> India.
> Phone No. +91 1596 255652, Mob. No. +91-7709129400,
> Email: vaibhav.dixit.pilani.bits-pilani.ac.in, vaibhavadixit.gmail.com
> http://www.bits-pilani.ac.in/pilani/vaibhavdixit/profile
> https://www.linkedin.com/in/vaibhav-dixit-b1a07a39/
>
> ORCID ID: https://orcid.org/0000-0003-4015-2941
>
> http://scholar.google.co.in/citations?user=X876BKcAAAAJ&hl=en&oi=sra
>
> P Please consider the environment before printing this e-mail
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>


--
Regards,
Dr. Vaibhav A. Dixit,
Visiting Scientist at the Manchester Institute of Biotechnology (MIB), The
University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
AND
Assistant Professor,
Department of Pharmacy,
▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄
Birla Institute of Technology and Sciences Pilani (BITS-Pilani),
VidyaVihar Campus, street number 41, Pilani, Rajasthan 333031.
India.
Phone No. +91 1596 255652, Mob. No. +91-7709129400,
Email: vaibhav.dixit.pilani.bits-pilani.ac.in, vaibhavadixit.gmail.com
​http://www.bits-pilani.ac.in/pilani/vaibhavdixit/profile
https://www.linkedin.com/in/vaibhav-dixit-b1a07a39/
ORCID ID: https://orcid.org/0000-0003-4015-2941
http://scholar.google.co.in/citations?user=X876BKcAAAAJ&hl=en&oi=sra
P Please consider the environment before printing this e-mail
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Fri Mar 06 2020 - 08:00:03 PST
Custom Search