Re: [AMBER] pH dependent calculation for Oligomers

From: Jason Swails <>
Date: Tue, 5 Jan 2016 07:29:27 -0500

On Tue, Jan 5, 2016 at 3:42 AM, Mijiddorj Batsaikhan <>

> Dear Jason,
> Thank you for your reply, I want to simulate separate simulations in 0.5
> intervals.

​I'm not sure why you want to do this, but such an approach is unlikely to
yield as much information as you'd hope by simply using H++ or PROPKA to
assign protonation states for your simulation. The difference between your
pH environments is too small to, in general, to have much effect on the
"dominant" protonation state of each residue. Furthermore, with so many pH
values, you are almost certain to try a pH that is close to the pKa of some
of your residues. As a result, no single set of protonation states will
accurately represent the "correct" ensembles at those pHs.

If, for some reason, you need to simulate the behavior of your system in a
range of pHs with 0.5 interval, then pH-REMD is really your best option.
Note that this is really an advanced option, and you should familiarize
yourself with the underlying theory before blindly attempting a
simulation. There is a tutorial for CpHMD at
and a pH-REMD tutorial at​

​But you should evaluate exactly what you are trying to learn from your
study in order to design an experiment to test your hypothesis. The H++
server is useful if you want to determine protein behavior in "general" pH
environments (e.g., "high" pH, "low" pH, or neutral pH), but any simulation
that uses a fixed set of protonation states is really representative of an
ensemble over a pH *range*.​ [1]

I tried to use H++ server for oligomer pdb structure. I have got
> FAILURE caused by multiple chains. I could not fix this error. I thought
> that if I use H++ server for single chain and I find out which each amino
> acid's ionization state and then I use the ionization state to the multiple
> chains. Is it possible?

​Sure, that's one approach. The approximation degrades as the interactions
between the chains become stronger (particularly between the titratable
residues). As with any decision, you should evaluate the effect of this
approximation (which will depend on your system).


[1] Protonation state and pH are thermodynamically coupled variables, like
pressure and volume or temperature and energy. Holding one fixed by
definition allows the other to fluctuate.

Jason M. Swails
Rutgers University
Postdoctoral Researcher
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Received on Tue Jan 05 2016 - 04:30:03 PST
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