[gmx-users] Pulling a CG protein

[David van der Spoel]

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, so if these are wrong, CG models are 
hopeless...

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