[gmx-users] surfactants simulation topology generation with Automated Topology Builder and lincs warnings

Thomas Piggot t.piggot at soton.ac.uk
Fri Aug 18 17:53:02 CEST 2017

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.



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.

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