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: [email protected]
[[email protected]] on behalf of
Peter Kroon [[email protected]]
Sent: 17 August 2017 12:03
To: [email protected]
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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