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

Thomas Piggot t.piggot at soton.ac.uk
Fri Aug 18 17:26:17 CEST 2017

Hi Emiliano,

So I had a spare 5 mins and I found your molecule on the ATB:


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.



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.

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