[gmx-users] Pulling a CG protein

[XAvier Periole]

On Jul 30, 2009, at 12:10 PM, David van der Spoel wrote:

> XAvier Periole wrote:
>> On Jul 30, 2009, at 11:40 AM, David van der Spoel wrote:
>>> Marc Baaden wrote:
>>>> Hi Xavier (and Johnny),
>>>> I quite agree with what Xavier says. Still I would like to point  
>>>> out
>>>> that we have used CG models to pull on them and at least  
>>>> qualitatively
>>>> they behave quite reasonably, although these models have never been
>>>> parameterized or systematically tested with this kind of  
>>>> application in
>>>> mind.
>>> In general models that have been parameterized for one specific  
>>> observable may not reproduce other observables *unless* the  
>>> observables used for parameterization have a clear physical basis  
>>> *and* the energy function captures the correct physics. Most  
>>> biomolecular force fields (including Martini as far as I know)  
>>> have been parameterized to reproduce density and energy of  
>>> condensed phase (liquids), and hence this kind of data is usually  
>>> reproduced quite well. However mixtures of components (e.g. two  
>>> liquids) are usually not reproduced as well.
>>>
>>> By doing the kind of pulling simulations, preferably both  
>>> atomistic and with CG models, one can try to verify whether the CG  
>>> models can actually reproduce force curves to a comparable  
>>> accuracy as all atom models. This kind of work should be done  
>>> *systematically* before any applications.
>>>
>>> What does this boil down to? If you want to apply MD tools to get  
>>> an accurate force curve *now*, use all atom models. If you want to  
>>> play with and test CG models, then do a large systematic test  
>>> (many systems). If the CG models perform reasonably, you have  
>>> cleared everyone's conscience and will get a lot of citations. If  
>>> they don't then you should try to understand why not. Are there  
>>> fundamental flaws in the model? If so, can they be fixed?
>> This is of course the idea, but then comes the problem of believing  
>> that atomistic simulations
>> are actually giving the right answer!
>
> Of course, on the other hand CG models were developed to a large  
> extent by comparison with A models,
Yes on data from A models that were compared to Exp data, so as much  
reliable as possible :))
> so if these are wrong, CG models are hopeless...

Well now we use CG to (re)parameterize AT models ... just kidding ...
> In addition, especially for this kind of applications, does the  
> experimental data measure the same thing that we try to calculate?
>
> Questions, questions.
>
>>> Have fun.
>>>
>>>> What I mean by qualitatively is that I wouldn't trust a force- 
>>>> extension
>>>> curve of such simulations (unless you do some force-matching :))  
>>>> - re:
>>>> FD144), but the conformational changes that are observed in a  
>>>> moderate
>>>> pulling regime do seem to make sense.
>>>> The experiments we carried out were interactive pulling  
>>>> experiments,
>>>> either to induce opening and closure of the guanylate kinase  
>>>> enzyme or
>>>> to explore the membrane anchoring and the mechanical properties  
>>>> of the
>>>> SNARE complex. This is briefly described in reference [1].
>>>> Cheers,
>>>> Marc
>>>> [1] http://dx.doi.org/10.1002/jcc.21235
>>>>   O. Delalande, N. Férey, G. Grasseau and M. Baaden:
>>>>   Complex Molecular Assemblies at hand via Interactive Simulations,
>>>>   2009, J. Comp. Chem.
>>>> x.periole at rug.nl said:
>>>>>> Hi Johnny,
>>>>>> I am not familiar with pulling and even less with gromacs but I  
>>>>>> would
>>>>>> be very cautious in using the MARTINI force field for the kind of
>>>>>> simulation you are doing. This CG model has not been tested at  
>>>>>> all
>>>>>> for this and it might not be very good at it! But I would be very
>>>>>> interested in knowing how it   actually perform.
>>>>>> XAvier.
>>>
>>>
>>> -- 
>>> David van der Spoel, Ph.D., Professor of Biology
>>> Molec. Biophys. group, Dept. of Cell & Molec. Biol., Uppsala  
>>> University.
>>> Box 596, 75124 Uppsala, Sweden. Phone:    +46184714205. Fax:  
>>> +4618511755.
>>> spoel at xray.bmc.uu.se    spoel at gromacs.org   http://folding.bmc.uu.se
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>
>
> -- 
> David van der Spoel, Ph.D., Professor of Biology
> Molec. Biophys. group, Dept. of Cell & Molec. Biol., Uppsala  
> University.
> Box 596, 75124 Uppsala, Sweden. Phone:	+46184714205. Fax: +4618511755.
> spoel at xray.bmc.uu.se	spoel at gromacs.org   http://folding.bmc.uu.se
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