[gmx-users] Ligand Parameters

[Mark Abraham]

David Mobley wrote:
> Justin,
> 
>> 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.

To take the example of CHARMM (with which I'm most familiar) there are 
lots of (e.g.) dihedral parameters that are very insensitive to the atom 
types at the four positions. Since an aromatic CH group in benzene is 
isoelectronic with an aromatic N and an aromatic O+, I don't think this 
analogy is too bad. You can even test the assumption by comparing the 
first two atom types (and maybe NH+ too) but you need to be careful that 
the dihedrals aren't equivalent by construction... I would be 
parameterizing my bonds and angles for aromatic C-O+ in the fashion 
David describes below though.

> 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.

Amen.

Mark