Re: [AMBER] ph md simulation

From: Jason Swails <>
Date: Fri, 08 Nov 2013 07:22:17 -0500

On Fri, 2013-11-08 at 10:00 +0000, Necmettin Pirinccioglu wrote:
> Dear Users,
> I have an organic compound with 8 titratable groups. I try to do constant
> pH (CpHMD) MD simulation but I could not create cpin file. I wonder if anyone could help me on this or direct me to a similar work.

This may be a _very_ challenging project. Your best bet is to break
your organic compound into different fragments and parametrize each of
those fragments (which will become separate residues).

The Amber 12 manual has some tips on running constant pH MD on a custom
residue, but I'll outline the general procedure here.

1) You will need to derive charges for each of the fragments for every
protonation state, taking care to keep the any atoms within 2 bonds of
the 'connections' with other fragments the same charge in every
protonation state. R.E.D. can help you parametrize the charges subject
to the necessary constraints.

2) You will need to generate 'model' compounds for each of the fragments
that are properly capped where they connect to other fragments.

3) You need to use TI (or some other alchemical FE method, like FEP or
H-REMD) to compute the reference energy between each of the protonation

4) You will need to add the charge state for every fragment (residue)
you parametrized above along with their corresponding reference energies
to $AMBERHOME/AmberTools/src/etc/cpinutils/ (look at the
other residues defined in that file for examples of how to do this).

After those 4 (somewhat complicated and involved) steps, you will be
able to generate the cpin file. Then you will need to titrate each of
the model compounds you designed in step 2 to make sure the reference
energies are correct. Finally, you'll need to titrate the whole organic
compound and make sure those results seem reasonable as well (it's very
easy to derive charges in such a way that CpHMD will not work).

Before getting started with any of these steps, it will help immensely
to be intimately familiar with Mongan's paper describing constant pH MD.

Good luck,

[1] John Mongan, David A. Case, and J. Andrew McCammon, "Constant pH
molecular dynamics in generalized Born implicit solvent", J. Comput.
Chem., 2004, 25 (16), pp. 2038-2048

Jason M. Swails
Rutgers University
Postdoctoral Researcher
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Received on Fri Nov 08 2013 - 04:30:05 PST
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