[gmx-users] CHARMM36 - Smaller Area per lipid for POPE - Why?

Thu Aug 2 15:25:22 CEST 2012

Hi Sebastien,

I have not tested POPE, but I have tested in detail DPPC and POPC. 
Because of this I cannot be certain of your issue. The only differences 
in your setup to what I generally use is I use rcoulomb of 1.2 and rlist 
of 1.2 (with the 0.8/1.2 vdw switching).

There are differences in the way that GROMACS switches off the van der 
Waals interactions, compared to how it is normally done in CHARMM and so 
this may be impacting upon your simulation. That said, using a very 
similar setup to yours I have found this impact to be generally fairly 
minimal (but again not with POPE).

The only other reason that I can think of is that simulation in the 
Klauda paper just may not have converged (the POPE area per lipid in 
Figure 5 of this paper does look like it might potentially still be 
decreasing).

If I were you, I would perform some simulations of the POPE membrane in 
either NAMD or CHARMM. This way you can be sure that the area per lipid 
you are seeing is not due to any differences in simulation codes.

Sorry I can't be of more help.

Cheers

Tom

Sebastien Cote wrote:
> Dear Gromacs users,
> 
> I did new tests on the POPE membrane with CHARMM36 parameters, but I still always get area per lipid values that are smaller than experimental value by 4 to 6 Angstrom2. Here are my new tests. 
> 
> My initial configuration is an equilibrated POPE membrane with 80 lipids at 1 atm and 310K in NPT. It was taken from Klauda's website and it was obtained from the study in which the POPE parameters were tested (Klauda, J. B. et al. 2010 J. Phys. Chem. B, 114, 7830-7843).
> 
> I use TIPS3P (Charmm's special TIP3P). My simulations parameters are similar to those used in a previous tread on the Gromacs mailing list (http://lists.gromacs.org/pipermail/gmx-users/2010-October/055161.html for DMPC, POPC and DPPC of 128 lipids each) :
> 
> dt = 0.002 ps; rlist = 1.0 nm; rlistlong = 1.4 nm; coulombtype = pme; rcoulomb = 1.4 nm; vdwtype = switch or cutoff (see below); DispCorr = No; fourierspacing = 0.15 nm; pme_order = 6; tcoupl = nose-hoover; tau_t = 1.0 ps; ref_t = 310K; pcoupl = Parrinello-Rahman; pcoupltype = semiisotropic; tau_p = 5.0 ps; compressibility = 4.5e-5; ref_p = 1.0 atm; constraints = h-bonds; constraint_algorithm = LINCS. Nochargegrps was used when executing pdb2gmx. 
> 
> The simulation time of each simulation is 100 ns. I tried different VdW cutoff values, since it was previously mentioned that cutoff values for VdW may influence the area per lipid. The average value and standard deviation are calculated on the 20 to 100 ns time interval. 
> 
> 1- For VdW switch from 0.8 to 1.2 nm : The area per lipid is 54.8 +/- 1.6 A2.
> 2- For VdW switch from 1.1 to 1.2 nm : The area per lipid is 54.6 +/- 1.8 A2.
> 3- For VdW cutoff at 1.4 nm :          The area per lipid is 55.9 +/- 1.6 A2.
> 
> I also checked the influence of DispCorr with VdW switch from 0.8 to 1.2 nm : 
> 
> 1- Without DispCorr : The area per lipid is 54.8 +/- 1.6 A2.
> 2- With DispCorr :    The area per lipid is 54.4 +/- 1.9 A2.
> 
> I also checked the influence of PME cutoff with VdW switch from 0.8 to 1.2 nm :  
> 
> 1- For PME cutoff at 1.4 nm : The area per lipid is 54.8 +/- 1.6 A2.
> 2- For PME cutoff at 1.0 nm : The area per lipid is 56.4 +/- 1.5 A2.
> 
> These values are smaller than 4-6 A2 when compared against the experimental value (59.75-60.75 A2) and the value obtained in Klauda's simulation (59.2 +/- 0.3 A2). DispCorr and LJ cutoff weakly impact the results. Reducing the PME cutoff seems to have the greatest effect, but the value obtained is still smaller than experimental value by 3-4 A2. 
> 
> I also tried other initial configurations, but the results were either very similar or worst. 
> 
> Larger membrane gave similar results for the mean values and smaller standard deviations. 
> 
> -------
> 
> Have anyone else tried to simulate a CHARMM36 POPE membrane in Gromacs? Do you get similar results?
> 
> Is a 3-4 A2 deviation from experiment likely to influence my membrane/peptide simulations? Would it then be preferable to go with CHARMM27 in the NPAT ensemble?
> 
> At this point, I have no clue of how to reproduce correctly Klauda's results for POPE. Any suggestion is welcomed. 
> 
> Thanks,
> 
> Sebastien 
> 
> 
> ----------------------------------------
>> Date: Mon, 23 Jul 2012 16:06:40 -0500
>> From: pcl at uab.edu
>> To: gmx-users at gromacs.org
>> Subject: Re: [gmx-users] CHARMM36 - Smaller Area per lipid for POPE - Why?
>>
>> On 2012-07-23 02:34:31PM -0300, Sebastien Cote wrote:
>>> There is not much difference when using DispCorr or not. At least on the same time scale as the simulation with switch cutoff from 0.8 to 1.2 nm and on the same time scale.
>>>
>>> Should DispCorr be used in all membrane simulations? I thought that we should always use this correction.
>> I alwasy thought it was actually forcefield dependent. I never use it with
>> CHARMM since the mdp files I used as the basis for mine didn't with C27, and
>> I get acceptable APL with POPC when using the same mdp with C36. I haven't
>> compared the codes for CHARMM to see if dispcorr is builtin to the gromacs
>> implementation or not, but the reason I brought it up is that on past
>> mailing list discussions about TIPS3P, there were reports of significant
>> density differences with and without dispcorr.
>>
>>
>>> Thanks,
>>>
>>> Sebastien
>>>
>>> ----------------------------------------
>>>> Date: Fri, 20 Jul 2012 12:47:44 -0500
>>>> From: pcl at uab.edu
>>>> To: gmx-users at gromacs.org
>>>> Subject: Re: [gmx-users] CHARMM36 - Smaller Area per lipid for POPE - Why?
>>>>
>>>> Did you play with DispCorr?
>>>>
>>>> On 2012-07-20 09:46:13AM -0300, Sebastien Cote wrote:
>>>>> Dear Gromacs users,
>>>>>
>>>>> My simulations on a POPE membrane using the CHARMM36 parameters are giving ''area per lipid'' values well below the experimental value (59.75-60.75 Angstroms2). Is their someone else experiencing a similar problem? If yes, how did you solved it?
>>>>>
>>>>> I did the following :
>>>>>
>>>>> I used the CHARMM36 parameters kindly provided by Thomas J. Piggot on the Users contribution section on Gromacs website.
>>>>> My starting configuration was taken from : http://terpconnect.umd.edu/~jbklauda/research/download.html
>>>>> It is a POPE membrane of 80 lipids equilibrated in NPT at T=310K and P=1atm for 40 ns. It is taken from the article Klauda, J. B. et al. 2010 J. Phys. Chem. B, 114, 7830-7843.
>>>>>
>>>>> At first, I tested normal TIP3P vs. CHARMM TIP3P and saw that normal TIP3P gives smaller Area per lipid of about 2-3 Angstroms. This was also observed by T.J. Piggot (personnal communication) and Tieleman (Sapay, N. et al. 2010 J. Comp. Chem. 32, 1400-1410). So, I will present only the simulations using CHARMM TIP3P. As in Klauda's paper, my simulations are at 310K and 1 atm. As them, I used a switch cutoff for vdw, and I used normal cutoff for PME. The simulations are 20 ns. I can send my .mdp file for more details. I varied the switch condition on vdw :
>>>>>
>>>>> 1- For a switch from 0.8 to 1.2 (as in Klauda's paper), I got Area per lipid of about 56.5 Angstroms2; whereas they got 59.2 in their paper, matching the experimental value of 59.75-60.75.
>>>>> 2- For a switch from 1.0 to 1.2, I got Area per lipid of about 53.5 Angstroms2, which is smaller than the previous cutoff. This is surprising since a previous thread on gromacs-users mailing lists said that increasing the lower cutoff, increased the Area per lipid or had not impact on POPC of DPPC.
>>>>> 3- For a switch from 1.1 to 1.2, I got Area per lipid of about 55 Angstroms2.
>>>>> 4- For a hard cutoff at 1.4, I got Area per lipid of about 52 Angstroms2.
>>>>>
>>>>> I also tried to re-equilibrate the membrane in the NPAT ensemble for 10 ns at 310K and 1 atm. Then, when I launched the simulation in NPT, I ended up with different results :
>>>>>
>>>>> 1- Switch from 0.8 to 1.2 gave a smaller area per lipid of 54 Angstroms2.
>>>>> 2- Switch from 1.0 to 1.2 gave a larger area per lipid of 55 Angstroms2.
>>>>> 4- Hard cutoff at 1.4 gave a similar area per lipid of 52.5 Angstroms2.
>>>>>
>>>>> I looked at the POPE paramaters for CHARMM36 in Gromacs, and they agree with the published parameters.
>>>>>
>>>>> Am I doing anything wrong? Is their someone else experiencing a similar problem for POPE? If yes, how did you solved it?
>>>>>
>>>>> Should I instead use CHARMM27 parameters in the NPAT ensemble? I want to study the interaction between a peptide and the POPE membrane. I am troubled that the NPAT ensemble might influence my results in a bad way. Also, I can not use OPLS AA nor GROMOS for the protein interactions because these force fields are not giving the correct structural ensemble for my peptide in solution.
>>>>>
>>>>> I am willing to send more information if you need.
>>>>>
>>>>> Thanks a lot,
>>>>> Sincerely,
>>>>>
>>>>> Sébastien --
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>>>> --
>>>> ==================================================================
>>>> Peter C. Lai | University of Alabama-Birmingham
>>>> Programmer/Analyst | KAUL 752A
>>>> Genetics, Div. of Research | 705 South 20th Street
>>>> pcl at uab.edu | Birmingham AL 35294-4461
>>>> (205) 690-0808 |
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>>>>
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>> ==================================================================
>> Peter C. Lai | University of Alabama-Birmingham
>> Programmer/Analyst | KAUL 752A
>> Genetics, Div. of Research | 705 South 20th Street
>> pcl at uab.edu | Birmingham AL 35294-4461
>> (205) 690-0808 |
>> ==================================================================
>>
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-- 
Dr Thomas Piggot
University of Southampton, UK.