Ion Concentration Force Fields

Do I understand you have decided to use unmodified Charmm36 ion parameters now? To reply to your original question: I don’t understand why you think you need to change parameters to change concentration. That is not needed at all.

I can also add that I would not expect Na and CL to have a significant effect on proteins, even at high concentration. Other ions might significant effects.

Yes, I found that this was unnecessary and simply used CHARMM36 with NBIX (no changes).

And thank you for your input, I will also look into other ions that may have more significant effects.

When achieving a specified concentration, I usually replace water molecules with the ions. I notice that at extreme concentrations (above 1M) there reaches a point where there are no more water molecules that can be replaced for my current box size. Is the only solution to increase box size? Or is there some other method of reaching a certain concentration?

I am getting the ‘No more replaceable solvent!’ error.

@jalemkul Going off of this topic, is re-equilibrating the system referring to re-running nvt or npt equilibration using the output simulation files rather than the nvt or npt files? I am slightly confused as to how to re-equilibrate. Any resources that you may have would be appreciated. Thank you.

“Re-equilibrate” just means “start over.”

I see. To be clear, as in if the simulation is ongoing, I continue further by making a new tpr file from scratch and using the cpt file?

I’m not sure I understand the question. Extending a simulation is a straightforward process ( and does not require a new .tpr file “from scratch.” Extending a simulation is unrelated to the question at hand of adding something new and re-starting.

Thank you for your reply. I am able to extend the simulation. I apologize for the confusion, I was asking in terms of whether continuing is related to restarting as you had said. So if a simulation is at 50ns and I restart, is the simulation back at 0ns? Or is what I add beginning from 50ns? As in, does using a new tpr file “from scratch” continue the simulation from where I left off?

If you continue a simulation using a checkpoint file, you resume from the exact point in time that the checkpoint file was written. A new .tpr file, on its own, starts from time zero unless you provide a .cpt file to mdrun -cpi, which then continues from that time point and completes as many steps as remain in the .tpr file.

I see, thank you for the clarification. So, in a sense ‘re-equilibrating’ would just mean getting rid of any sort of premature crystallization in the system by running through each equilibration step again to write a new tpr file, and then proceed with the simulation resulting in one cohesive period of time. I want to be sure I understand this concept correctly.

In a sense, yes, but if we return to the original issue, high salt concentration can lead to contraction of the system due to the introduction of void space. You can minimize and equilibrate this system, but the box will possibly have compressed substantially such that you no longer have a system at the desired concentration; it will be higher. If you then increase the box size and add more water, you have effectively perturbed an equilibrated system, which then requires additional equilibration. That’s what I’m referring to by “starting over” - you don’t have the system you thought you did, so you have to change it and then equilibrate to resolve the fact that you’d have a high concentration central volume and a pure water layer around the system.

Thank you. I see, yes that does make sense. In order to quantify this and to monitor the system is it fair to simply check the pressure? This does seem to fluctuate substantially even in only water. Or are there additional methods of quantifying contraction of a system?

Contraction of the box will be apparent by monitoring density or the box vectors. Pressure is too noisy to use and in any case is driven by the barostat.

I understand. To tell compression is there a certain ratio between starting density and current density that would indicate the compression? Or is there a set density value that indicates compression?

No. Density will go up, box vectors will decrease.

Thank you very much. This has been a great help. May the density fluctuate, though? Would it be a clear upward increase? I am trying to better understand these relationships.

Also, where may I find resources in addition to the GROMACS website to better understand these phenomena? I would like to get a better perspective on the technicalities as well.

Every quantity in an MD simulation fluctuates. The original phenomenon that I referred to would be an obvious shift in the value.

This is just the stuff you learn by experience. The first time I built a 2 M salt solution, the box contracted by a ton and the final concentration was well over the desired value. I added water, re-equilibrated, and everything was fine.

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Can we avoid this contraction of box in this way
Suppose we do not use gennion command . Instead we will calculate how much molecules of ions and water is needed to reach the desired concentration in a given box volume. And then use co-ordinate files of water and ions to put those number of molecules in the box. This way we don’t have to replace the water molecules and can have better control over denisty.

@neetish possibly, but you may run into atomic clash issues trying to fill the box via gmx insert-molecules. If you try to add ions by inserting them into a pre-equilibrated box of water, that certainly won’t work given the spacing of water and the typical ion-water (oxygen) distances.