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mittko Offline OP
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I am wondering if the ADP, ATP, AMP nucleotides have been parametrized in different protonation states? No oxygen belonging to any of the phosphate groups has a proton in the current "toppar_all27_na_nad_ppi.str" file. I cannot find a patch either. There is a residue:

RESI PPI2 -2.00 ! Inorganic phosphate, protonated, adm jr.

but could I use it somehow (partial charges) to generate a topology for, say, ADP, with a terminal protonated phosphate?

Basically, the question is: are there already paramerized protonation states of these nucleotides and if not, would it be safe to parametrize "by analogy" rather than to perform some kind of single point/QM?

Thanks.


Last edited by mittko; 04/20/10 05:33 PM.
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There's some additional protonation states in "toppar_all27_na_model.str". Perhaps you can find what you need there...

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mittko Offline OP
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Thanks, but I do not think that I see protonation states of these nucleotides or patches. There are a few methylphosphate residues, but I do not know how exactly I can use them. In this case, what would the best approach to parametrize these molecules with protons on certain oxygens?

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Take a close look at the charges on these methylphosphates. Compare to the charges on the larger compounds (ADP, ATP, AMP,...). Do you notice anything? How do you think the charges on the larger model compounds were determined?

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mittko Offline OP
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Of course, I have noticed the similarities, and I can manually tweak the charges in a similar fashion, but manual manipulation involves more or less personal interpretation, which could not be justified by quantitative measures. Do you suggest, for example, to get the charges of the phosphate groups from RESI PPI2 (stream/toppar_all27_na_nad_ppi.str) and put them on ADP in order to obtain the single protonated state of ADP? Similarly, would the charges of RESI MP_1 (stream/toppar_all27_na_model.str) give me the protonated state of AMP?

If this is sufficient (and apparently quite easy to do), is there a reason why protonation states of these nucleotides have not been added or at least patches included in the topology sets?

Thanks.

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It is often difficult to reliably determine charges on larger model compounds. For this reason, we perform the actual charge optimization on small model compounds (like those methylphosphates) and transfer them to the larger compounds. There are rules for doing so; for instance, if we delete a hydrogen to form a bond with another atom, we most commonly sum the charge on the hydrogen into its parent atom. I haven't looked at it very closely, but from a distance, it appears that all the phosphate charges in the nucleic acid force field were derived from the methylphosphate charges using this rule. If you want to be sure, you could have a look at the nucleic acid force field paper. If you construct topologies for your desired compounds using the same rules, there's no reason why they should be less valid than our topologies...

Originally Posted By: mittko
If this is sufficient (and apparently quite easy to do),
I think it is, but double-check the paper to be sure.

Originally Posted By: mittko
is there a reason why protonation states of these nucleotides have not been added or at least patches included in the topology sets?
No idea, but my best guess is that at some time, the decision was taken to publish the force field - sitting in front of the computer and parameterizing more model compounds without end won't get any bills paid. The published force field contains the most common compounds and protonation states, as testified by the fact that it's widely used.


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