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

edesantis edesantis at roma2.infn.it
Fri Aug 18 17:40:05 CEST 2017

thanks a lot Tom,

I've used gromocs 53a6 ff, the united atom topology and the original 
do you used the same parameters?

should I use the optimised geometry file??

thank again for your precious help


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.

Emiliano De Santis

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