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#33831 - 04/22/14 07:33 AM CHARMM Parameterization of porphyrin
Jim Parker Offline
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Registered: 04/22/14
Posts: 2
Hello,
I am attempting to develop a parameterization set (force field) for a free-base (no metal center) porphyrin. I started from the heme molecule that can be found in the CHARMM36 parameter files. However, the inclusion of an iron atom at the core compared to my metal-free case, should significantly affect the partial charges as well as bond strengths.

According to the CGenFF FAQs, the paradigm is to break the molecule into smaller segments, generate parameters, and then synthesize the full molecule. There are several reasons for this suggestion; in addition to reducing contaminating secondary interactions, fragmentation reduces heavy atom counts, which is essential for some of the high level QM calculations.

But I guess my concern is the "contaminating secondary interactions". The porphyrin core is key to the simulations I'm going to be running. The large aromatic ring structure shares electrons in a non-trivial manner, and I thought the point of re-parameterizing was to accurately estimate the partial charges and bond/torsion strengths that were generated by these secondary interactions.

I'm using a tool ffTK (description at http://www.ks.uiuc.edu/Research/vmd/plugins/fftk/ ) to assist building the QM calculations required to simulate the interaction of the water with the molecule in order to determine the partial charges. However, when simulating the water moving radially away from one of the interior atoms of the porphyrin core, the water molecules move too close to the atoms on the opposite side. I can move the line of interaction out of the plane of the molecule, but I'm not sure how that would affect the QM calculations for charge. Any guidance?

Alternatively, I can just use pyrrolidine as a base unit for all tetra-pyrroles in the molecule, but as mentioned would be concerned it oversimplifies the charge distribution.

Suggestions?

Cheers,
--Jim Parker

Physics and Astronomy Department
The University of Texas at San Antonio

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#33832 - 04/22/14 12:53 PM Re: CHARMM Parameterization of porphyrin [Re: Jim Parker]
Kenno Offline
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Registered: 12/19/05
Posts: 1535
Loc: Baltimore, MD
Originally Posted By: Jim Parker
However, when simulating the water moving radially away from one of the interior atoms of the porphyrin core, the water molecules move too close to the atoms on the opposite side.
That's exactly what I mean with secondary interaction. This is a very blatant case even; they are often more subtle than that.

Originally Posted By: Jim Parker
I can move the line of interaction out of the plane of the molecule
That would be an unvalidated approach, and the few times we tried it, the results were mediocre at best. This water interaction-based charge optimization is pretty empirical business and it's a bit brittle with regard to small deviations from the protocol.

Originally Posted By: Jim Parker
Alternatively, I can just use pyrrolidine as a base unit for all tetra-pyrroles in the molecule, but as mentioned would be concerned it oversimplifies the charge distribution.
Using atom-centered point charges is already a gross oversimplification of the charge distribution. In comparison, I don't think your loss of large-scale resonance will make your simulation results significantly worse, at least for the neutral protonation state. For the positive ones, it does become an important issue. The latter is a bit of an unsolved problem, though I think I can offer some workarounds if need be. Luckily, porphyrin is not very basic (I think), so the problem might not be a relevant one.

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#33837 - 04/23/14 07:45 AM Re: CHARMM Parameterization of porphyrin [Re: Jim Parker]
Jim Parker Offline
Forum Member

Registered: 04/22/14
Posts: 2
Kenno,
Thank you for the insight. You are correct that porphyrin is not very basic, and more importantly to me ;), the case I'm examining requires a neutral porphyrin core.

Moving on to the simulation phase. Again, thanks.

Cheers,
--Jim

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