[gmx-users] Re: Phosphate esters

Justin A. Lemkul jalemkul at vt.edu
Wed Nov 2 21:25:41 CET 2011

Ben Ahmady wrote:
> 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.

I would say that similarity only gets you so far.  A phosphodiester between two 
equivalent groups (generic R substituents, for this exercise) will have 
different charges from the same group in a PC headgroup due to the very strong 
dipole present in the latter species.  Careful charge calculations according to 
the prescribed methodology should produce reasonable results.  The key, of 
course, is in the validation.  A model is only as good as it proves itself to be.



Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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