Re: [AMBER] Can we combine amber and gaff atom types?

From: Aditya G Rao <>
Date: Thu, 3 Nov 2016 18:39:58 +0200

Dear Carlos and David,
Thanks a lot for the suggestions and the explanation!

.David: What exactly do you mean by, " As needed you may distribute the
excess charge this imparts to the sulfur and the first carbon on the
pyrrole to get the net charge back to (-1)"?

Thanks in advance!

On Wed, Nov 2, 2016 at 10:44 PM, David Cerutti <> wrote:

> ^ Agree with Carlos, the interface between parameter sets should be
> minimal. This is what I was getting at further down in my novella--take
> ff14sb atom types for everything up to perhaps the sulfur on the side
> chain. Now if we can retain the charges up to CB (type 2C) we can ensure
> that the ff14sb backbone behavior (which is where the most effort has been
> done) stays put. That's what we can focus on now. First, reference
> amino12.lib in the $AMBERHOME/dat/leap/lib directory and mirror the charges
> for ACE, NME, and the modified CYS up through CB. As needed you may
> distribute the excess charge this imparts to the sulfur and the first
> carbon on the pyrrole to get the net charge back to (-1).
> To get the best parameters for ff14sb you will need to refit charges on the
> pyrrole group and sulfur while retaining the other charges that correspond
> to atoms ff14sb does describe. I wouldn't recommend trying to map the
> pyrrole atom types to ff14sb equivalents: that thing has chemical groups
> that aren't in proteins, which puts you in a different ball park. As soon
> as you need new atom types, they might as well be called "plain", salted",
> and " honey roasted," so the goal here is to invest an appropriate amount
> of effort to make something compatible with the rest of your protein. The
> central dogma of ff14sb is "Hartree Fock 6-31g* charges, with bonded
> parameters to mimic a vacuum phase MP2 / cc-pvTZ potential energy surface"
> and that's what we'll do.
> One thing I didn't realize when I first replied is that your modified amino
> acid is BIG. The first capability we need is to be able to make plausible
> conformations of your nonstandard residue. Cysteine covalently bonded to
> not just one ring system but a macrocycle of four! This is going to create
> a challenge, but what it means is that you may want to trim away the excess
> before trying new parameter development. *My advice would be this: take
> bond and angle parameters from our libraries, decide on charges for the big
> system, then create a stripped-down, tiny system and try to develop the
> torsion parameters for the pyrrole :: ethanethiol interface.* In what
> follows I'm providing detailed instructions to carry out that idea.
> First, take bond and bond angle parameters straight from ff14SB or GAFF,
> using Carlos's logic: these parameters are derived prior to charge fitting
> and can, in most protocols, be taken as given. They're also more
> consistent across different atom types ({2C, CT, 3C}-CT-N, etc.)--the
> different atom types largely come from our efforts to get increasingly
> accurate torsions in slightly different chemical situations, but when we do
> that we typically just clone the bond and bond angle parameters from their
> root types (2C, 3C, and CX are all from CT). Just find the best matches
> you can based on your chemical intuition, probably based on the ff14SB
> methionine residue, and apply the stiffness and equilibrium parameters to
> the new atom types at the pyrrole :: SG-CB interface.
> Next, charges: if after reassigning the charges of the Cysteine up to SG,
> you only need to change the charge of that sulfur by 0.1e to maintain the
> integer net charge, I think you're set. (The charge on sulfur is never
> well resolved by our methods--the thing's got quadrupoles that our
> nuclear-centered charges simply can't do very well, so R-S-R' sulfur atoms
> in methionine and other situations always get assigned very small charges
> because the least squares solution is to give it no significant monopole,
> forfeiting whatever higher order multipoles would be better.) Otherwise, if
> you can find out how to make the RED server give you the charges you need
> for the SG and nearest atoms on the tetrapyrrole, you're set. If neither
> of those solutions works, I can hit it with mdgx and see about getting you
> a reasonable charge model directly from HF/6-31g*.
> Finally, the torsion parameters: for this, you should excise one pyrrole
> ring from your macrocycle, put CH3 blocking groups on either end where the
> macrocycle got cut, and attach -S-CH2-CH3 to the other side. Then, do the
> same trick of assigning ff14SB atom types to the S-CH2-CH3 atoms (i.e. use
> 2C for the carbon of CH2, CX for the carbon of CH3, and H1 for all
> hydrogens on CH2 or CH3) and the atom types of your larger Cys-Pyrrole
> system for the pyrrole ring. Once you have that small molecule, just
> assign it the standard AM1-BCC charges (again, I'm counting on the sulfur
> getting a pretty small, flat charge asssignment). And keep the bond and
> bond angle assignments from your larger Cys-pyrrole, but set the torsion
> amplitudes involving the sulfur to zero (you're going to make a new frcmod
> for this representation of the linker system in the same way it seems you
> have for your Cys-pyrrole already). Now you've got a model system which
> can move in the ways you need to see the joint between your larger Cysteine
> and pyrrole moving. Once you've got that, I think the easiest solution is
> to use the new mdgx routines to generate a handful of conformations (about
> 60 I'd guess), and computations at the MP2/cc-pvTZ level will take about an
> hour each on a single CPU to get their single point energies--an afternoon
> with a couple of machines. With the conformations of your test system and
> their single point energies in hand, it is a five minute exercise to fit
> the torsion parameters appropriate for the links between the ff14SB and
> GAFF components of your system.
> Last, you collect all of these bond, bond angle, and torsion parameters
> into a frcmod and take the charges and ff14SB/GAFF atom types in your
> .prepi or .lib file for the full cys-pyrrole, and you're ready to do your
> simulation.
> Keep in touch, I'll do what I can to help.
> Dave
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Aditya G. Rao
PhD Student
Fritz Haber Research Center for Molecular Dynamics
Institute of Chemistry, HUJI
Givat Ram, Jerusalem, Israel
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Received on Thu Nov 03 2016 - 10:00:02 PDT
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