Re: [AMBER] The resonable way how to protonate protein for Amber simulation in explicit water ?

From: Marek Maly <>
Date: Wed, 21 Apr 2010 19:29:39 +0200

Dear Jason,

thanks a lot for your comments !

Regarding to H++ sw I thaught that it is well known and used in Amber
community since it is
one of the useful SW listed on Amber page (please see "Related software
that interfaces with Amber").
The direct link is:

I think that physics background for H++ and "Amber MD under constant pH"
to protonation is probably the same or very similar.

I think that compatibility of internal dielectric constant in H++ and
Amber if one
uses H++ for protonation is important question and would be nice to have
satisfactory answer.

Intuitively it seems that changing internal dielec. in H++ from default 6
to 1
is resonable but I am not sure about since maybe there could be some small
in algorithms and the result obtained in H++ with internal diel. constant
6 regarding to
protonation states might be the same like results obtained for example
during Amber MD under constant
pH with internal diel. 1 (again just regarding to protonation).

Of course that this could be answered (at least regarding concrete
molecule) with several trials.

OK, I have last question.

Regarding to MD under constant pH in Amber, which molecules are
automatically protonated here
according to given pH and actual conformation. Only proteins ?

Thanks again !



Dne Wed, 21 Apr 2010 15:35:38 +0200 Jason Swails <>

> Hello,
> 2010/4/20 Marek Maly <>
>> Dear all,
>> just a quick technical question. I am just wondering
>> what is the recommended way of preparing protein structure
>> for simulation in explicit water under given pH.
>> If I am not wrong, in this case simulation under constant pH
>> has to be approximated by simulation with fixed "correspondent"
>> protonation state of the given protein. Am I right ?
> Yes. Explicit MD is not yet supported under constant pH MD, so you will
> have to choose a constant protonation state.
>> If yes, what is the recommended procedure for protein protonation
>> respect to given pH ?
> I think it really depends on the system. If you're simulating a
> solvent-exposed carboxylate at pH 7, this is really a no-brainer for the
> most part. If you're looking at a buried residue or something with a pKa
> relatively close to the pH, it's a more complicated issue.
>> It is for example sufficient to use just H++ server to assign
>> protonation
>> states
>> to all ionisable groups regarding to given pH and of course regarding to
>> the given
>> (representative) protein conformation ?
> This seems reasonable to me. However, like you mentioned, this will not
> take into account (as far as I know), conformational-dependent pKa
> shifts.
> Another option, of course, is to run constant pH MD using sander and take
> the protonation states dominant throughout that simulation for your
> explicit
> simulation. This approach would be more "correct", though it certainly
> takes a little bit longer to decide on protonation states (though it's
> probably the best approach for complex systems.
>> Speaking about H++ it is OK to keep their default value of internal
>> protein
>> dielectric constant which has the
>> value 6 or one have to change it to value 1 which is the only
>> recommended
>> value in any Amber implicit solvent
>> calculation including MM/PBSA which I would like to carry out with my
>> protein/X complex after explicit water MD ?
> I don't know anything about this software, so I can't comment here.
>> Thanks a lot in advance for any valuable comments/experiences !
>> Best wishes,
>> Marek
> Good luck!
> Jason
> ---------------------------------------
> Jason M. Swails
> Quantum Theory Project,
> University of Florida
> Ph.D. Graduate Student
> 352-392-4032
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Received on Wed Apr 21 2010 - 11:00:05 PDT
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