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.
--
Emiliano De Santis
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