AMBER Archive (2008)

Subject: Re: AMBER: questions about run MD at different pH

From: David A. Case (
Date: Mon Mar 03 2008 - 23:07:00 CST

On Mon, Mar 03, 2008, Kailee wrote:
> 1) If I protonate my protein (which is solvated in water explicitly) with
> H++ program at different pHs and then run them in AMBER as normal, at which
> pH will be my protein simulating? will it be the pH value I set in H++
> program OR there is a fixed pH for all simulations in AMBER?

There is no "fixed pH for all simulations": you would get behavior
corresponding to the (fixed) protonations chosen by H++. This might roughly
correspond to a fixed pH, but still involves an unphysical *fixed* set of
protonation states.

> 2) I have read the manual about constant pH calculations, which can be used
> for simulations at different pH, right? however, it's only for implicit
> solvent simulations, and I would like to ask, is there any other differences
> with this method except it can't be used for explicit solvent, for example,
> I have some non-standard residues ( which I have created frcmod file for
> them), will these be OK with the method? and are there any differences in
> analysis methods?

Non-standard residues are a "problem" in the sense that you will have to work
hard to understand the details of how the code works, so that you can adapt
your residues to them; (assuming that your non-standard residues have
protonataed and de-protonated forms.)

> 3) Will it be possible that I manually add some H+ or OH- ions to change the
> pH conditions? and if yes, how should I do it? should I add them in leap or
> include them in the pdb file? and after the addition of those (H+/OH-),
> should I still neutralise the system (using PBC)?

No, this is not possible. Even if you could create a water box big
enough [**] to allow you to simulate an H+ concentration of 10**-7 M,
molecular mechanics potentials don't allow chemical changes, so the
protons could not bond to (or dissociate from) the acids and bases in
your solute.

[** Note that if you had one H+ and one OH- ion, you would need about 50
million water molecules to construct a solution with pH=7.]


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