normal Parameterizing new molecule

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3 years 5 months ago #5348 by Prunotto
Parameterizing new molecule was created by Prunotto
Hi everybody,

I am trying to parameterize a new lipid, which is not currently present in the MARTINI database.

For doing this, I am following the general outline that is provided in www.cgmartini.nl/index.php/tutorials-gen...rzining-new-molecule , where the toluene is taken into consideration as general example.

At step 1) ("Generate atomistic reference data"), you guys say that for toluene, 1 ns of simulation would be enough for sampling, as it is a quite simple molecule.

My molecule is quite more complicated: specifically, it is a lipid with 4 tails (therefore, the general structure is similar to cardiolipins) and it is composed by 288 atoms (hydrogens included). The MARTINI model that I created and that I am trying to parameterize is composed by 28 MARTINI beads.

Based on these data, can you estimate how long my simulation should be to be able to sample the bonds and angles accurately enough? Do you think that 40-50 ns would be enough?

Thanks a lot for the great job that you are doing! All the best!

Alessio

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3 years 4 months ago #5355 by helgi
Replied by helgi on topic Parameterizing new molecule
Sadly it’s impossible to tell just from the size of the molecule. We commonly use 50-200 ns long AA simulations as our reference lipid simulations, so I would recommend you extend yours somewhat. You can get some idea of your convergence by looking at the bonds/angles/dihedrals over time and make sure you are sampling all states frequently.

As a side node, you need to beware that your AA simulation only represents that specific condition (lipid phase, other lipid types in your simulation, temperature, etc) so if you want to make a general Martini lipid parameters it is a good idea not to over-fit, try to use similarity to already parameterized lipids, and/or do reference simulations under different conditions.

Hope this helps,
Cheers,
- Helgi

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3 years 4 months ago #5365 by Prunotto
Replied by Prunotto on topic Parameterizing new molecule
Yes, it was definitely very useful! Thank you very much about this!

I hope I am not bothering you too much, but I would still have a couple of questions:

1) I see from your tutorial that the atomistic simulations from which you sample the states, have a sampling frequency of about 1 frame every 1 ps. Is this necessary, or I can decrease a bit this sampling frequency? In general, is there a recommended sampling frequency or it depends by multiple factors?

2) The lipid that I have to parametrize in MARTINI will eventually be used to create a membrane. In this case, which solvent should I use to simulate my all-atom lipid?
As a matter of fact, it is true that the solvent that I will use in the MARTINI simulations is water, but since I will create a membrane patch, the lipid will spend all the time into a hydrophobic environment (the membrane itself).
In other words, if I simulate the all-atom lipid into water, will this simulation be able to capture the hydrophobic behaviour of the lipid tails?

I would like to thank you again and I'm looking forward to receiving your reply.

All the best,

Alessio

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3 years 4 months ago #5366 by helgi
Replied by helgi on topic Parameterizing new molecule
1) yep you can normally reduce the sampling frequency when you extend the simulations time (e.g. so long as you end up with well sampled conformational distributions)

2) This will depend. Normally you could do a short AA simulation of one lipid in water just to see the “flexibility” of the lipids under those conditions. But your main AA reference simulation would be under “normal” conditions (as close as you can to those you want to use the lipid/molecule in. If this is a simple bilayer forming lipid e.g. POPC you can simulate a pure POPC bilayer. If this is a none bilayer forming lipid or a lipid that normally is in low quantity I would rather have simulate it in a reference bilayer (e.g. 5-20% of you lipid in a POPC bilayer or a bilayer similar to the one you want to simulate at the CG level).

Cheers,
- Helgi

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2 years 3 months ago #7121 by yogi@martini
Replied by yogi@martini on topic Parameterizing new molecule
Hi friend,
I think there is a typo error in this tutorial, the statement "Remember that S-beads only have a small radius compared to other S-beads and will thus have the same partitioning free energy (between water and octanol) as normal beads." is confusing, did you mean to say "Remember that S-beads only have a small radius compared to other beads and will thus have the same partitioning free energy (between water and octanol) as normal beads."

What exactly the physical reasoning behind S-beads having small radius.

Thanks in advance.

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2 years 3 months ago #7124 by riccardo
Replied by riccardo on topic Parameterizing new molecule
Yes, that's a typo. We'll correct it asap, thanks for spotting it.

Regarding the physical reasoning behind the S-beads, the have a smaller radius as they describe 3 or 2 non-hydrogen atoms instead of 4.

Please make sure to check also the section about ring particles in S. J. Marrink et al., J. Phys. Chem. B, Vol. 111, No. 27, 2007.

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2 years 2 months ago #7193 by yogi@martini
Replied by yogi@martini on topic Parameterizing new molecule

helgi wrote: 2) This will depend. Normally you could do a short AA simulation of one lipid in water just to see the “flexibility” of the lipids under those conditions. But your main AA reference simulation would be under “normal” conditions (as close as you can to those you want to use the lipid/molecule in. If this is a simple bilayer forming lipid e.g. POPC you can simulate a pure POPC bilayer. If this is a none bilayer forming lipid or a lipid that normally is in low quantity I would rather have simulate it in a reference bilayer (e.g. 5-20% of you lipid in a POPC bilayer or a bilayer similar to the one you want to simulate at the CG level).

Cheers,
- Helgi


Hi Helgi. Thanks for the reply. But I could not get what you want to say. I am rephrasing the question. Suppose I have Atomistic simulation data for bilayer in water. And I want to build CG model for the lipid which forms the given bilayer, actually my plan is once I get correct CG model, I will self assemble it and see whether is forms the similar bilayer. To get bond and angle distribution should I do atomistic simulation of single lipid in water or not? OR should I analyze each and every lipid in given atomistic bilayer to get bond angle distribution. OR something else we need to do.

Thank you. Looking forward to get reply from you.

-Yogi

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2 years 1 month ago #7199 by helgi
Replied by helgi on topic Parameterizing new molecule
Sadly the answer is that you have should do both and most likely even more simulations, depending on how generalizable you want you lipids to be, and then also adjust the CG model to fit exp. values.

If you only run an AA bilayer simulation and parameterize your CG lipids to fit those, matching all angles / bond / dihedrals closely, you can tune them to get really good match between the lipid properties at both resolutions.

Now e.g. you raise the temperature (or take one lipid out into water) then your AA lipids will behave differently due to their new environment but your CG lipids not so much as you have looked them in place / over fit them to that specific AA reference environment. So it all depends on what you want to do and there is always a tradeoff.

Hope this helps,
- Helgi

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