[gmx-users] surfactants simulation topology generation with Automated Topology Builder and lincs warnings
edesantis
edesantis at roma2.infn.it
Sat Aug 19 12:45:29 CEST 2017
yes, that is the problem,
at the beginning everything seem to be ok, but letting the simulation
run for some tens of ns (to have enough statistic), I have the LINCS
warnings,
so I will try to build manually the topology using the GROMOS ff
building blocks, us you suggested,
thank you again for your help
bye,
Emiliano
On 2017-08-18 18:58, Thomas Piggot wrote:
> Letting the simulation run for a bit longer, I also get LINCS warnings
> after several ns. The issues seem to arise for the sugar part of the
> molecule. This doesn't hugely surprise me, as this part of the ATB
> topology is quite odd with the non-polar hydrogens included for the
> sugar rings (unlike in the normal sugar/carbohydrate GROMOS force
> fields).
>
> You probably will need to go down the route that I suggested
> previously and manually make the topology though a combination of
> building blocks available within the GROMOS force field(s).
>
> Cheers
>
> Tom
>
> On 18/08/17 16:52, Thomas Piggot wrote:
>> I used the optimised pdb but I can't imagine it would change anything.
>> I also used the united-atom topology and the GROMOS 54A7 force field
>> files (the ones from the ATB the also include the parameters for the
>> HS14 atom type). I'm pretty sure (IIRC) that there aren't any force
>> field changes from 53A6 to 54A7 so as to have influenced your
>> simulations of the molecule.
>>
>> Cheers
>>
>> Tom
>>
>> On 18/08/17 16:39, edesantis wrote:
>>> thanks a lot Tom,
>>>
>>> I've used gromocs 53a6 ff, the united atom topology and the original
>>> pdb,
>>> do you used the same parameters?
>>>
>>>
>>> should I use the optimised geometry file??
>>>
>>>
>>> thank again for your precious help
>>>
>>> Emiliano
>>>
>>>
>>>
>>> On 2017-08-18 17:26, Thomas Piggot wrote:
>>>> Hi Emiliano,
>>>>
>>>> So I had a spare 5 mins and I found your molecule on the ATB:
>>>>
>>>> https://atb.uq.edu.au/molecule.py?molid=223816#panel-md
>>>>
>>>> Simulating one of these in water doesn't give me any problems with a
>>>> 2
>>>> fs timestep, so you should check the starting structure of your
>>>> system
>>>> and also your simulation procedures.
>>>>
>>>> Cheers
>>>>
>>>> Tom
>>>>
>>>> On 18/08/17 14:46, Thomas Piggot wrote:
>>>>> You shouldn't use PRODRG, well the default output at least (e.g.
>>>>> see http://pubs.acs.org/doi/abs/10.1021/ci100335w).
>>>>>
>>>>> The ATB is generally pretty good, and although it might not be
>>>>> perfect here (e.g. as you have sugars in your structure which have
>>>>> been pretty heavily optimised in different variants of the GROMOS
>>>>> force field; see
>>>>> http://onlinelibrary.wiley.com/doi/10.1002/jcc.24229/abstract and
>>>>> http://pubs.acs.org/doi/abs/10.1021/ct300479h amongst other
>>>>> papers), I'd be pretty surprised that the topology is causing LINCS
>>>>> warnings/crashes. If it were me, I'd definitely simply the
>>>>> situation to begin with and look at one of your surfactants in
>>>>> water. This will help you ensure your starting structure is fine
>>>>> and also allow you to determine exactly what bit of the system is
>>>>> causing the crashes.
>>>>>
>>>>> Cheers
>>>>>
>>>>> Tom
>>>>>
>>>>> On 18/08/17 14:10, edesantis wrote:
>>>>>> Hi,
>>>>>>
>>>>>> thank you for both your suggestions,
>>>>>>
>>>>>> as Tom, I also think that the structure of the surfactant could be
>>>>>> modified by the presence of other surfactants in the aggregate
>>>>>> form, maybe it is not and only the non bonded parameters can have
>>>>>> a role in the formation of the aggregates (I am quite a beginner
>>>>>> of these kind of simulation...)
>>>>>>
>>>>>> anyway my all atomistic simulation has double purpose,
>>>>>> firstly, since it was the first time I used an ATB created
>>>>>> topology, I wanted to see if the topology well reproduced the
>>>>>> aggregations of these kind of surfactants,
>>>>>> and secondly, I want to use the bonds and angles distribution to
>>>>>> parametrize my Martini model, and see again if also the Martini
>>>>>> model can reproduce similar aggregates to those seen in the aa
>>>>>> simulation
>>>>>>
>>>>>>
>>>>>>
>>>>>> I've tried to continue the simulation using dt=0.00182 ps and
>>>>>> after a while there are lincs warnings, so it smells like a bad
>>>>>> parametrization of the all-atomistic topology, as Tom said.
>>>>>> till now I've always simulated standard proteins, so I don't know
>>>>>> how to parametrize the force field for these small molecules, I am
>>>>>> now trying PRODRG (once I have the token to use it), if you have
>>>>>> other suggestion are welcome....
>>>>>> for gromos sugar ff, do you have any reference??
>>>>>>
>>>>>>
>>>>>>
>>>>>> for what concern the needed to introduce this kind of molecules,
>>>>>> I think it is quite necessary, these surfactants, use to
>>>>>> solubilize the proteins in the crystal, are forming micelles
>>>>>> around them and, since the final goal of my Martini simulation is
>>>>>> the reproduce the diffuse scattering in the crystals, I think it
>>>>>> is quite important to reproduce all the crystal components in
>>>>>> order to have a system that is more similar to the real condition.
>>>>>>
>>>>>>
>>>>>>
>>>>>> thank you again
>>>>>> Emiliano
>>>>>>
>>>>>>
>>>>>> On 2017-08-18 14:22, Thomas Piggot wrote:
>>>>>>> Hi Peter,
>>>>>>>
>>>>>>> I'd imagine that in particular the CG angle parameters between
>>>>>>> beads
>>>>>>> may well be different if you determined them by mapping on to a
>>>>>>> single
>>>>>>> one of these surfactants in water, compared to mapping onto an
>>>>>>> ensemble of structures in an aggregated state as the hydrophobic
>>>>>>> chains would try to 'fold up' and bury themselves away from the
>>>>>>> water.
>>>>>>> I haven't actually tried this though, that's just how I think it
>>>>>>> would
>>>>>>> probably be. Nice and easy to test anyway, if Emiliano really
>>>>>>> does
>>>>>>> need to parameterise this molecule.
>>>>>>>
>>>>>>> Cheers
>>>>>>>
>>>>>>> Tom
>>>>>>>
>>>>>>> On 18/08/17 09:04, Peter Kroon wrote:
>>>>>>>> Hi Tom,
>>>>>>>>
>>>>>>>>
>>>>>>>> thanks for your thoughts :)
>>>>>>>>
>>>>>>>> I want to respond to your sampling argument: I figured that a
>>>>>>>> surfactant
>>>>>>>> in solution is "more free" to sample conformations due to
>>>>>>>> sterics than
>>>>>>>> one in an aggregated state, and that sampling would therefore be
>>>>>>>> faster.
>>>>>>>> Your point of sampling the bonded conformations from a solvated
>>>>>>>> vs an
>>>>>>>> aggregated state is a powerful one though (then again, shouldn't
>>>>>>>> the
>>>>>>>> difference in aggregated state vs solvated state come from the
>>>>>>>> non-bonded parameters? i.e. the bonded parameters should be the
>>>>>>>> same for
>>>>>>>> both).
>>>>>>>>
>>>>>>>>
>>>>>>>> Peter
>>>>>>>>
>>>>>>>>
>>>>>>>> On 17-08-17 21:10, Piggot T. wrote:
>>>>>>>>> Hi Peter/Emeliano,
>>>>>>>>>
>>>>>>>>> I'm not sure I agree with some of what Peter says, but I guess
>>>>>>>>> it's probably a matter of taste. If it were me, I'd definitely
>>>>>>>>> want my atomistic simulations to behave properly before trying
>>>>>>>>> to develop CG parameters based upon these simulations. I know
>>>>>>>>> that the coarse-graining will lose some of the detail, but I'd
>>>>>>>>> want all of the detail in the atomistic simulations to be as
>>>>>>>>> accurate as possible to hopefully develop reasonable CG
>>>>>>>>> parameters with the appropriate detail lost but the underlying,
>>>>>>>>> correct, behaviour retained. You cannot be sure of this in your
>>>>>>>>> case here.
>>>>>>>>>
>>>>>>>>> As for the sampling in the atomistic simulations, I guess you
>>>>>>>>> mean you could run one in a box a lot quicker as the system is
>>>>>>>>> smaller? With 50, you obviously have more surfactants in there
>>>>>>>>> to give you a lot more data for the parameterisaton and as a
>>>>>>>>> larger simulation size should scale better, you probably will
>>>>>>>>> get better sampling (in terms of stats) with the 50 in a box
>>>>>>>>> setup. Plus you get to also check, as Emeliano said, that the
>>>>>>>>> atomistic simulations behave sensibly and aggregate/form
>>>>>>>>> micelles, etc. (whatever this surfactant does). You can also
>>>>>>>>> look for differences in the CG bonds/angles depending upon what
>>>>>>>>> state the molecule is in (solvated, aggregated, etc.). For this
>>>>>>>>> specific case, I guess this may not matter if it's only one
>>>>>>>>> bound to a protein though.
>>>>>>>>>
>>>>>>>>> Anyway, regarding the original post, I would firstly ask is it
>>>>>>>>> really necessary to have this molecule in the simulations? I
>>>>>>>>> couldn't tell from the post why this was wanted to be included.
>>>>>>>>> Is it an important ligand, or is it just in the experimental
>>>>>>>>> structure as an artefact of the crystallisation
>>>>>>>>> conditions/procedure (which I suspect is quite likely)? If it's
>>>>>>>>> the latter, there is no need to go to all this effort. As for
>>>>>>>>> the LINCS warnings, it's hard to exactly say without seeing the
>>>>>>>>> topology/starting structure. It could well be that the ATB
>>>>>>>>> topology for things like the sugars isn't that great (the
>>>>>>>>> GROMOS sugar force fields are heavily optimised for things like
>>>>>>>>> dihedrals), or it could potentially be an issue with the
>>>>>>>>> starting structure of the system. If it were me, I would likely
>>>>>>>>> make the atomistic parameters manually through combining the
>>>>>>>>> building blocks available within the GROMOS force field.
>>>>>>>>>
>>>>>>>>> Cheers
>>>>>>>>>
>>>>>>>>> Tom
>>>>>>>>>
>>>>>>>>> ________________________________________
>>>>>>>>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se
>>>>>>>>> [gromacs.org_gmx-users-bounces at maillist.sys.kth.se] on behalf
>>>>>>>>> of Peter Kroon [p.c.kroon at rug.nl]
>>>>>>>>> Sent: 17 August 2017 12:03
>>>>>>>>> To: gromacs.org_gmx-users at maillist.sys.kth.se
>>>>>>>>> Subject: Re: [gmx-users] surfactants simulation topology
>>>>>>>>> generation with Automated Topology Builder and lincs warnings
>>>>>>>>>
>>>>>>>>> Hi Emeliano,
>>>>>>>>>
>>>>>>>>>
>>>>>>>>> since you're just going to use the atomistic simulation to get
>>>>>>>>> some
>>>>>>>>> parameters for your CG model, I don't think the differences
>>>>>>>>> will be
>>>>>>>>> significant --- the approximations your are going to make in CG
>>>>>>>>> will be
>>>>>>>>> larger anyway. I would even argue you'll be better off if you
>>>>>>>>> run just
>>>>>>>>> one surfactant in water to get your bonded parameters, rather
>>>>>>>>> than 50,
>>>>>>>>> since sampling will be better.
>>>>>>>>>
>>>>>>>>> For further validation of your Martini model, you can (should)
>>>>>>>>> look at
>>>>>>>>> some more macroscopic properties as well, such as dimerization
>>>>>>>>> free
>>>>>>>>> energy and partition free energy.
>>>>>>>>>
>>>>>>>>>
>>>>>>>>> Peter
>>>>>>>>>
>>>>>>>>>
>>>>>>>>> On 17-08-17 11:18, edesantis wrote:
>>>>>>>>>> dear gromacs users,
>>>>>>>>>>
>>>>>>>>>> I have a problem in the simulation of a surfactant, Octyl
>>>>>>>>>> Glucose
>>>>>>>>>> Neopentyl Glycol, that is present in protein crystals.
>>>>>>>>>>
>>>>>>>>>> my goal is to have a coarse grained model for this surfactant
>>>>>>>>>> with
>>>>>>>>>> Martini ff.
>>>>>>>>>> to do that I have to generated an all atomistic simulation to
>>>>>>>>>> use as a
>>>>>>>>>> reference to build the Martini topology.
>>>>>>>>>>
>>>>>>>>>> I've downloaded the pdb file https://www3.rcsb.org/ligand/37X
>>>>>>>>>> of the
>>>>>>>>>> surfactant and since there is not an existent ff for the all
>>>>>>>>>> atom
>>>>>>>>>> simulation, I've generated it from ATB web site
>>>>>>>>>> (https://atb.uq.edu.au/) for gromos 53a6 united atoms
>>>>>>>>>> parameters set.
>>>>>>>>>>
>>>>>>>>>> I've built a cubic box of 7 nm of side, I've put inside the
>>>>>>>>>> box 50
>>>>>>>>>> surfactant molecules and then I've solvated it with spc water.
>>>>>>>>>> then after a minimisation with the sd both in vacuum and in
>>>>>>>>>> the
>>>>>>>>>> presence of the solvent, I proceeded with a md in the NVT
>>>>>>>>>> ensemble,
>>>>>>>>>> with dt=0.002 ps
>>>>>>>>>> the problem is that I received several lincs warnings and the
>>>>>>>>>> simulation stops.
>>>>>>>>>> so I've decreased the dt to 0.0015 ps and the simulation ends
>>>>>>>>>> without
>>>>>>>>>> problem, I've continued it increasing the dt to 0.0018 for
>>>>>>>>>> 20ns, and
>>>>>>>>>> than to 0.00183 ps and there are not any kind problem.
>>>>>>>>>> but when I try to increase dt to 0.00186 the lincs warning
>>>>>>>>>> problems
>>>>>>>>>> came again.
>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>> watching the simulation movie with vmd, I can see that the
>>>>>>>>>> surfactants
>>>>>>>>>> form an aggregate (as they should do), and it seems to me that
>>>>>>>>>> there
>>>>>>>>>> is not an apparent weird behavior.
>>>>>>>>>>
>>>>>>>>>> should I have to continue to increase the dt with small
>>>>>>>>>> increments
>>>>>>>>>> (i.e. 0.0002ps at each run) or can I just trust to the results
>>>>>>>>>> I have
>>>>>>>>>> (angles and bonds distributions) using the dt=0.00183 ps??
>>>>>>>>>> could the problem of the lincs warning arise from the
>>>>>>>>>> generation of
>>>>>>>>>> the topology with ATB??
>>>>>>>>>>
>>>>>>>>>> thank you in advance
>>>>>>>>>> Emiliano
>>>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>
>>>>>>> -- Dr Thomas Piggot
>>>>>>> Visiting Fellow
>>>>>>> University of Southampton, UK.
>>>>>>
>>>>>
>>>>
>>>> -- Dr Thomas Piggot
>>>> Visiting Fellow
>>>> University of Southampton, UK.
>>>
>>
>
> --
> Dr Thomas Piggot
> Visiting Fellow
> University of Southampton, UK.
--
Emiliano De Santis
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