[gmx-users] validation of ligand parametrization

Mark Abraham Mark.Abraham at anu.edu.au
Wed Jan 26 13:25:54 CET 2011

On 26/01/2011 11:10 PM, mohsen ramezanpour wrote:
> Dear Justin
> I don't want to rely on PRODRG server as others.
> I want to do my work as accurate as possible.
> Absolutely I read your papar and I know PRODRG present bad results for 
> estimating free energies.
> I want to parametrize my drugs by GROMOS43A1 parameters as you said.
> I know completely how to do it.Thanks for your and other user's guidances.
> Actually I couldn't find any experimentally data to try to obtain it's 
> result.Then i have to
> do what you said.(re-evaluating force field choice and .....)

Sounds wise.

> Can you please say me more about this method?

It sounds to me like he's said plenty of useful things on the topic :-) 
A question with a precise focus is much more likely to attract 
somebody's interest. Otherwise, it can sound too much like you're asking 
for your work to be done for you!

Back on point, if you can't determine a basis for the kind of empiricism 
GROMOS forcefields require, then you may want to choose one of the other 
force fields with a more automated method. That doesn't remove the need 
to validate, or the conundrum if validation fails, however. It's very 
easy to do a worthless simulation. Many of them are. Many more of them 
become so because they don't describe enough detail that they could be 
reproduced. For example, lots of people say just "I used PME with x 
cutoff" in the same way they did in the 1990s when they used a plain 
cutoff. I've read three such in the last week. However, that statement 
is almost useless as an indicator of quality in the electrostatic model. 
(Oops, I've digressed. Oh well.)


> Did you have something like this in your papers?
> Thanks in advance for your reply
> On Wed, Jan 26, 2011 at 3:14 PM, Justin A. Lemkul <jalemkul at vt.edu 
> <mailto:jalemkul at vt.edu>> wrote:
>     mohsen ramezanpour wrote:
>         Dear All and specially Dear Dr.Justin
>         I generated parameters for a typical ligand.
>         now I want to validate it.
>         How can I do it?
>         Please let me know references for doing this.
>         Of course I have read the article by
>         Dr.Justin(Alzeimer),Unfortunately I couldn't understand it
>         completely and very good.
>     I will assume that you're still using one of the Gromos force
>     fields for your work.  Gromos parameterization relies on
>     reproduction of condensed-phase behavior, in theory, the
>     partitioning of the species of interest between hydrophobic and
>     aqueous media.  Ideally, you would calculate deltaG of hydration
>     in different media, but such information is not always readily
>     available. That's why I turned to an alternate approach in the
>     paper you mention, but one that holds in the same spirit of the
>     force field and for which I had experimental evidence with which
>     to compare.
>     If you don't have any suitable experimental data regarding your
>     ligand, you should re-evaluate your force field choice and
>     consider whether or not parameterizing a bunch of unknown
>     compounds is a viable approach.
>     I certainly cannot help you better if you simply say you don't
>     understand something.  What isn't clear?
>         Is there any other article who has done validation after
>         parametrization?
>     Some, but (unfortunately) not many.  Numerous authors seem to
>     blindly rely on PRODRG, which was the motivation behind our most
>     recent work (in JCIM, which I believe you said you've read).  See
>     the references therein for a few examples of attempts that have
>     been made to derive and validate proper parameters.  More rigorous
>     standards are really necessary to avoid potential inaccuracies in
>     these types of simulations.
>     -Justin
>         Thanks in advance for your guidance.
>     -- 
>     ========================================
>     Justin A. Lemkul
>     Ph.D. Candidate
>     ICTAS Doctoral Scholar
>     MILES-IGERT Trainee
>     Department of Biochemistry
>     Virginia Tech
>     Blacksburg, VA
>     jalemkul[at]vt.edu <http://vt.edu> | (540) 231-9080
>     http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>     ========================================
>     -- 
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