[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 

so I will try to build manually the topology using the GROMOS ff 
building blocks, us you suggested,

thank you again for your help


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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