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

From: Jason Swails <>
Date: Wed, 21 Apr 2010 09:35:38 -0400


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 M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Graduate Student
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Received on Wed Apr 21 2010 - 07:00:03 PDT
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