[gmx-users] Re: Phosphate esters

[Ben Ahmady]

Dear Justin
> Parameterization is a tough task, if done properly. If you find it 
> came easy, it's probably not right ;) It sounds like you're trying to 
> work backwards from PRODRG and correct the charges. While that can be 
> OK, if you've committed to using the Gromos96 force fields, I'd 
> suggest you work the other way around. Look into the literature and 
> see if anyone else has done anything similar - what force field did 
> they use? Was it successful? Frankly, the details of parameterization 
> for Amber, CHARMM, and OPLS are significantly more detailed than those 
> of the Gromos96 force fields, so you may actually find it easier to 
> use the QM methods described for those other force fields. The next 
> most significant issue is validation. You have to have some criteria 
> by which your new parameters are judged. Again, this is a reason why 
> Gromos96 can be tough, unless you have DeltaG of solvation for your 
> compounds, or suitable models thereof. There are alternatives, but 
> they're not significantly better. Reproducing some condensed-phase 
> criteria is common to all the force fields (some have additional QM 
> geometry requirements). 

Many thanks for the detailed response; I really appreciate it. I've 
enjoyed reading the papers you've contributed to.

I'm not really tied in with any particular force fields at the moment, 
and I am teaching myself how to use AMBER, which admittedly does seem to 
be a lot more amenable to novel 'residues', what with the GAFF. I 
haven't been able to find any parameters which people have used for 
phosphate esters in the literature, though as I said there's an 
abundance of them for phospholipids. The real problem is that I don't 
have enough experience to say that parameters relating to groups which 
appear in my molecules as well as, say, DPPC (e.g. PO4) are going to be 
similar enough. I will take your advice though and continue searching (I 
haven't been able to have a look at Lipidbook yet actually, but have 
e-mailed Professor Mark Sansom and he's said they're having server 
problems and hope to be back soon), and will start using AMBER in more 
earnest.


Best regards

Ben