Hi Gabriel,
just a thought: I've noticed that antechamber doesn't work with aromatic
rings specified as a sequence of double-single bonds. It failed in my
experience as well. Try replacing the bonds of the entire ring with
partial double bonds (bond order "ar" in the mol2 bond record).
Sasha
Gabriel Rocklin wrote:
> Dear Junmei and others,
>
> I am trying to parameterize various heterocyclic compounds using
> Antechamber, and I'm getting strange results. Nitrogen and Carbon atoms
> that I think should be classified as aromatic are being classified as
> non-aromatic sp2. This creates a problem for free energy calculations
> because the non-aromatic atoms have very weak dihedral parameters associated
> with them which allows incorrect conformations.
>
> I can't trace all the problems I'm seeing to a single issue, so instead I'll
> list several. In all the examples, I'm using the version of
> ATOMTYPE_GFF.DAT that you send me in February, linked below (is there
> something newer?)
> http://archive.ambermd.org/201002/0314.html
>
> First I have some questions about pyrrole and imidazole.
>
> 1) When I parameterize pyrrole.mol2 doing:
>
> antechamber -f pyrrole.mol2 -fi mol2 -o pyrrole.prepi -fo prepi
>
> The nitrogen is classified as type 'na', which is described in GAFF.dat as:
> "Sp2 N with three connected atoms" which is a non-aromatic atom type.
> Shouldn't this be classified as aromatic? (Pyrrole isn't actually a
> molecule I'm interested in, but this is one of the most basic cases of the
> issue I can find).
>
> 2) When I parameterize neutral imidazole.mol2 in the same way, the Ns have
> two different atom types. The deprotonated nitrogen is recognized as 'nc',
> which GAFF.dat says is aromatic ("Sp2 N in non-pure aromatic systems")
> whereas the protonated nitrogen becomes 'na', again not aromatic. If there
> were a substituent coming off this nitrogen (or both nitrogens, in an
> imidazolium derivative) these would be parameterized such that they could
> bend significantly out of plane of the ring because the N was not classified
> as aromatic. Should they be parameterized this way or is the atom type
> assignment wrong?
>
> Now some issues with fused ring systems...
>
> 3) Indole. The N in indole is classified as "na". Shouldn't this be
> aromatic?
>
> 4) Imidazopyridine vs Indole. This is the kind of fused ring system that
> I'm interested in and where I see real problems. In Imidazopyridine, N1
> (the same N as in Indole, except now deprotonated) is recognized as aromatic
> and classified as 'nc'. But the N bridging the ring systems is the
> non-aromatic "na". Several carbons also change atom type. In Indole, all
> of the carbons are 'ca', 'cc', or 'cd' (all aromatic). In Imidazopyridine,
> some carbons switch to 'ce', 'cf', and 'c2', none of which are aromatic.
> The "na" nitrogen bridging the rings means that the two rings actually have
> the flexibility to bend toward each other, rather than the entire molecule
> staying planar.
>
> 5) 4-azaindole vs 4-azaindolium. In 4-azaindole, everything except the
> protonated nitrogen is aromatic. As far as I know, it should be aromatic,
> but this seems like the same problem as above. However, in 4-azaindolium
> (both nitrogens protonated), several carbons become nonaromatic (c2). One
> of the nitrogens even becomes classified as NH ("Amine N connected one or
> more aromatic rings") which must be because it itself is not recognized as
> aromatic.
>
> The above nitrogen issues seem to all come from any nitrogen being bonded to
> three atoms not being recognized as aromatic. However, this doesn't seem to
> be the full extent of the problem, because even the carbons in
> Imidazopyridine and 4-azaindolium become non-aromatic. My main concern in
> all of this is the torsional parameters because I don't want my aromatic
> fused rings to be folding in on each other if they aren't supposed to be.
>
> I've attached mol2 files of all of these molecules to see if you can
> reproduce what I'm seeing, and in the hope that a fix can be found.
>
> Thanks,
> Gabriel Rocklin
> UCSF Shoichet/Dill Labs
>
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Received on Mon Sep 20 2010 - 14:00:08 PDT
