[gmx-users] Ligand Parameters

[Justin Lemkul]

David,

Thank you for the quick and detailed reply.  I thought that the analog approach
would be a bit too quick-and-dirty, anyway :-)  I will set to work on making
some new parameters based on the information you've provided, and I will likely
focus on compatibility with the GROMOS force fields.  Perhaps I will have
something useful to contribute in due time.  Thanks for the link to the script;
I know it will prove most useful.

Thanks agin,
Justin

Quoting David Mobley <dmobley at gmail.com>:

> Justin,
>
> > I am interested in simulating some small molecules that involve oxygen in
> > aromatic rings (which thus bears a +1 charge).  I tried to submit one of
> these
> > molecules to PRODRG, but got an error indicating that there were too many
> bonds
> > to O.  I thought this issue might arise, due to the unusual condition of
> the
> > oxygen (+1 charge, hybridization, etc.)  I have looked into the list to see
> if
> > anyone had come across a similar problem, but I can't find an explicit
> example.
> >  I realize this odd case is probably limited by the developed force field
> > parameters, which don't appear to include O+.  I have checked the *.atp
> entries
> > to confirm this.  I read on the archive that it might be possible to
> develop
> > parameters using the ffamber ports (which I have) and using ANTECHAMBER
> (which
> > I have used) to get partial charges.  I would then have to create some
> entries
> > in the applicable .rtp file, etc, and otherwise do a lot of reading in
> Chapter
> > 5 of the manual :-)
>
> Are you committed to a particular force field? For example, with
> PRODRG, you are stuck with GROMOS or whatever else it can output
> (hence, you would need to use the same force field for other elements
> in the system).. Also, the charges from there would have, (ahem),
> possible issues even if it would generate parameters for your
> molecule. For example, their FAQ page says,
>
> "Q: The atomic charges don't always come out right? A: This is a well
> known limitation. PRODRG works with the concept of charge groups,
> which are defined as a group of bonded atoms with an integer charge.
> E.g. -COO would have the C (with a slight positive charge) and the two
> O's (with an equal negative charge) in one "charge group" with the
> total charge being -1. Thus in order for PRODRG to assign atomic
> charges it needs to be able to recognise the charge groups first. This
> is particularly difficult in ring systems with nitrogens, and several
> charge group definitions (e.g. C-Cl) or still missing. I would
> definitely recommend that you check these charges before starting your
> 2 microsecond simulation."
>
> In other words, you can't count on the charges to be right (for
> example, this charge groups concept is rather questionable).
>
> As far as having worked with O+, I haven't. You could try running it
> through antechamber (specifying the -nc flag for your molecule) and
> see if it actually can generate parameters for it... If you can
> parameterize it with Antechamber, you can use our conversion script
> (http://www.alchemistry.org/FreeEnergyTools) to convert those to
> GROMACS format (for use with the AMBER ports to GROMACS). But I can't
> vouch for how Antechamber will work for something with O+.
>
> > I realize this problem is not trivial, and I don't expect an easy solution,
> but
> > I was wondering if anyone out there had worked with O+ in their molecules,
> and
> > if they had any advice or topology building blocks that I might use as a
> > template, seeing as none have been contributed online.
>
> Have you searched the literature? If there aren't O+ parameters in
> current force fields, I suppose you'll have to derive them yourself in
> a manner consistent with the force field you plan on using for the
> rest of your system (i.e. possibly from QM).
>
> > I have also considered submitting an analog of my compound to PRODRG
> (normal
> > aromatic ring instead of one containing O+) to get the dihedrals, etc. and
> then
> > re-calculating charges under ANTECHAMBER.  Any thoughts on that approach?
>
> Presumably dihedrals, etc are affected by the atom types,
> hybridization, etc. Sounds like a bad idea. If I were a reviewer on a
> paper that did this, I'd probably think it was an even worse way to
> parameterize something than the "make the parameters up based on
> chemical intuition" approach.
>
> The way to do this: Figure out what force field you want to use; look
> up how existing parameters for that force field were derived, and then
> do something consistent with that to get your new parameters. The
> procedure will be different depending  on the force field you want to
> use.
>
> Best wishes,
> David
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Justin A. Lemkul
Biochemistry
Alpha Chi Sigma, AI '04
Virginia Tech