[gmx-users] validation of ligand parametrization

[mohsen ramezanpour]

Dear Dr Mark
Thanks for your guidances.
I am sorry for my last question.My english is not very good,I hope I could
say what was in my mind not what you read :-)
by the way,Thanks for your attention and your reply.

On Wed, Jan 26, 2011 at 3:55 PM, Mark Abraham <Mark.Abraham at anu.edu.au>wrote:

>  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.)
>
> Mark
>
>
> 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> 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 | (540) 231-9080
>> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>>
>> ========================================
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