[gmx-users] Melting temperature for the lipid bilayer

Thu Nov 24 01:24:46 CET 2016

Hi Moshen,

PS lipids with the standard GROMOS54A7 force fields (which is what I'm 
assuming you mean but 53a7) are likely to not produce the correct 
behaviour of PS membranes. The GROMOS re-parameterisation of lipids for 
54A7 was primarily based upon the modification of the CH3 choline head 
group parameters for PC lipids to make them behave well (plus the 
inclusion of the commonly used 'Chiu' united-atom lipids charges). 
Therefore using the same parameters for PS is almost certainly not going 
to work well, i.e. very likely to incorrectly produce far too ordered or 
even gel like membranes when they should be in the liquid crystal phase. 
I can't be sure as I haven't explicitly tested DSPS, but I have been 
testing some different PS force fields and can provide some GROMOS based 
PS parameters (tested for POPS and DOPS) should you wish to use a GROMOS 
based force field which is reasonable for such membranes.

However, based upon the information you have provided, I can't be quite 
be sure of exactly what you are trying to do. If you are judging your 
CHARMM simulations based upon the fact that from your GROMOS simulations 
you can quickly make a gel or very ordered phase, I refer you to my 
above point about the accuracy of the GROMOS force field you are using. 
It doesn't surprise me that your GROMOS force field based simulations 
rapidly form gel or very ordered phases, as I think the parameters you 
may well be using for these simulations are likely to induce this due to 
force field deficiencies. In other words, the CHARMM simulations are 
likely to be behaving sensibly but your GROMOS ones not.

I also completely agree with and want to further re-iterate some of the 
points already made by Justin and Chris. Trying to quantify a phase 
transition temperature of a lipid membrane from a simulation is a very 
difficult task. This because both heating or cooling simulations won't 
likely be anywhere near slow enough to measure this accurately and also 
because simulations at different fixed temperatures will also still 
likely suffer from sampling problems.

As an aside, you need to make sure that for your different simulations 
(GROMOS or CHARMM), you are using appropriate simulation parameters 
(i.e. appropriate mdp's). Lipid membrane force fields in particular are 
very sensitive to van der Waals cut-off's, so you need to get this right 
before doing anything else.

Cheers

Tom

On 23/11/16 21:08, Mohsen Ramezanpour wrote:
> Lowering the temperature can push the system to gel phase or ordered phase
> quickly (this is based on my simulations using Gromos53a7 on DSPS).
>
> Besides, I used the same system for different temperatures. This initial
> structure was made by myself using genconf. So, it was not in
> perfect "liquid state".
> The approach for making the initial state would not be a problem as the
> same approach gave liquid_disordered phase using gromos53a7 ff in 353.
>
> In these simulations, I used the .mdp files suggested by Charmm-GUI, as
> well as .itp and .gro files for DSPS were also taken from Charmm-GUI
> output.
> I checked .mdp parameters with what suggested in recent articles as follows:
>
> http://pubs.acs.org/doi/abs/10.1021/acs.jctc.5b00935
> Everything seems okay regarding to parameters.
>
> Cheers
> Mohsen
>
> On Wed, Nov 23, 2016 at 1:37 PM, Christopher Neale <
> chris.neale at alum.utoronto.ca> wrote:
>
>> You started a run with a liquid state conformation and it formed a gel on
>> its own at 350K ? Fair enough. You're using the proper charmm force
>> switching and cutoffs?
>>
>> ________________________________________
>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se <
>> gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of Mohsen
>> Ramezanpour <ramezanpour.mohsen at gmail.com>
>> Sent: 23 November 2016 15:31:53
>> To: Discussion list for GROMACS users
>> Subject: Re: [gmx-users] Melting temperature for the lipid bilayer
>>
>> Hi Christopher,
>>
>> I took the second approach by running simulations for 5 different
>> temperatures of 5 degrees intervals. (350, 355, 360, 365)
>> I will not pick any specific temperature as melting T. However, I can see
>> the shift between 355 and 365 K, representative of going to a new phase
>> (Liquid_disorder) in 365 K.
>> Visualization is also enough to see that 350 is in gel phase.
>>
>> Cheers
>>
>> On Wed, Nov 23, 2016 at 12:28 PM, Christopher Neale <
>> chris.neale at alum.utoronto.ca> wrote:
>>
>>> I presume you're heating your bilayer up slowly to assess the melting
>>> temperature? This method will give you an estimated melting temperature
>>> that is equal to the true melting temperature of that Hamiltonian in
>>> simulation only if you go infinitely slowly. At finite heating speeds,
>> your
>>> observed melting temperature will be greater than or equal to the true
>>> simulation melting temperature.
>>>
>>> You have to go slower than you might expect. For instance, even 0.15 K/ns
>>> overestimates the melting temperature (on average, of course).
>>>
>>> On the other hand, if you're evaluating the Tm by running simulations at
>>> various constant temperatures and you call the Tm the temperature at
>> which
>>> you see 50% gel and 50% liquid dynamically interconverting many times
>> then
>>> your estimate should be correct for the Hamiltonian you selected (though
>> I
>>> expect this approach to be way beyond current computational abilities).
>>>
>>> ________________________________________
>>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se <
>>> gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of Mohsen
>>> Ramezanpour <ramezanpour.mohsen at gmail.com>
>>> Sent: 22 November 2016 16:40:08
>>> To: Discussion list for GROMACS users
>>> Subject: Re: [gmx-users] Melting temperature for the lipid bilayer
>>>
>>> It is worth mentioning that with Gromos53a7, the model was made by
>> merging
>>> head group and tails, I got T= 353 K for the right phase.
>>>
>>> On Tue, Nov 22, 2016 at 2:37 PM, Mohsen Ramezanpour <
>>> ramezanpour.mohsen at gmail.com> wrote:
>>>
>>>> Hi Justin,
>>>>
>>>> Comments interspersed.
>>>>
>>>> On Tue, Nov 22, 2016 at 1:18 PM, Justin Lemkul <jalemkul at vt.edu>
>> wrote:
>>>>>
>>>>> On 11/21/16 3:28 PM, Mohsen Ramezanpour wrote:
>>>>>
>>>>>> Dear gromacs users,
>>>>>>
>>>>>> Running simulation on a lipid bilayer made by Charmm-GUI, there is
>>> about
>>>>>> 24
>>>>>> degrees difference between the reported temperature in Avanti and
>> what
>>> I
>>>>>> see in my simulations for getting a liquid disordered (L_disorder)
>>>>>> bilayer.
>>>>>>
>>>>>>
>>>>> How are you quantifying the transition in the simulation?
>>>> Mainly by diffusion constant and diffusion graph. However, diffusion
>>>> constant, bilayer thickness and area per lipid all have a shift.
>>>> Order parameters are also higher for lower temperatures.
>>>>
>>>>>
>>>>> I am using all-atom Charmm36 FF for simulations.
>>>>> What is the lipid?
>>>>>
>>>> DSPS
>>>>
>>>>> I know that it is not possible to get an exact match between
>>> experimental
>>>>>> and simulation T values for L_alpha phase of bilayers, but I am not
>>> sure
>>>>>> if
>>>>>> these gap seems reasonable or there is something wrong in my
>>>>>> simulations. I
>>>>>> have checked the bonds in tails and apparently, everything looks fine
>>>>>> with
>>>>>> topology.
>>>>>>
>>>>>>
>>>>> A gap of 24 degrees is quite substantial.  I would not consider that
>>>>> outcome to be sufficiently accurate.
>>>>>
>>>> The melting temperature for DSPS is 68 centigrade (341 K). The
>>>> liquid_disordered one is about 365 K (at least one with reasonable
>>>> characteristics of liquid_disorder phase).
>>>>
>>>>> However, based on this, doing simulation in L_alpha phase requires
>>> hight T
>>>>>> values (close to 85 or 90 degrees of centigrade) which makes me worry
>>>>>> about
>>>>>> the water molecules in the system. It is a high temperature for water
>>>>>> molecules.
>>>>>>
>>>>>>
>>>>> Agreed, but TIP3P has a ton of other problems, so this is probably the
>>>>> least of our concerns at the moment.
>>>>>
>>>>> -Justin
>>>>>
>>>>> Its worth mentioning that bilayer structural properties like lipid
>> order
>>>>>> parameters match available experimental data for these high T values.
>>>>>>
>>>>>> Please let me know your opinion.
>>>>>>
>>>>>> Cheers
>>>>>> Mohsen
>>>>>>
>>>>>>
>>>>> --
>>>>> ==================================================
>>>>>
>>>>> Justin A. Lemkul, Ph.D.
>>>>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>>>>>
>>>>> Department of Pharmaceutical Sciences
>>>>> School of Pharmacy
>>>>> Health Sciences Facility II, Room 629
>>>>> University of Maryland, Baltimore
>>>>> 20 Penn St.
>>>>> Baltimore, MD 21201
>>>>>
>>>>> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
>>>>> http://mackerell.umaryland.edu/~jalemkul
>>>>>
>>>>> ==================================================
>>>>> --
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>>>>
>>>>
>>>> --
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>>>>
>>>
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>

-- 
Dr Thomas Piggot
Visiting Fellow
University of Southampton, UK.