[gmx-users] Decreased Area/Lipid of Lipid Bilayer for CHARMM-GUI

Tue Jun 14 20:12:19 CEST 2016

On 6/14/16 2:10 PM, Nidhin Thomas wrote:
> Hi Dr. Neale/ Dr. Lemkul,
>
> I have simulated DPPC bilayer for 12 nanoseconds now. The average APL is 0.608 nm^2 now with a standard deviation of 0.016.
> he initial dip in the APL (from 0.63 to 0.599) was found at the beginning of NPT itself.
>
> Therefore I think, I should just run more time and it should give a good result around 0.61 nm^2.
>
> Dr. Lemkul had given me the links of few research papers and in one of the paper, the surface area per lipid for DPPC bilayer was found out to be 0.604 +/- 0.1 nm^2 for force based switching functions for LJ interactions with 10-12 Angstrom cut-off .
>
> I do not know if 0.61 nm^ APL (from 0.63 nm^2) is an acceptable result for DPPC and I can continue analyze the results further.
>

12 ns is at least an order of magnitude shorter than what is normally necessary 
for membranes.  The result is not surprising and in good agreement with 
expectations.  But that doesn't mean the simulation is long enough; you just 
happen to have one quantity that works out well at this point.

-Justin

> Thanks a lot for helping me out,
>
> Nidhin Thomas
> University of Houston
>> ------------------------------
>>
>> Message: 3
>> Date: Tue, 14 Jun 2016 16:51:33 +0000
>> From: Christopher Neale <chris.neale at alum.utoronto.ca>
>> To: "gmx-users at gromacs.org" <gmx-users at gromacs.org>
>> Subject: Re: [gmx-users] Decreased Area/Lipid of Lipid Bilayer from
>> 	CHARMM-GUI
>> Message-ID:
>> 	<SN2PR03MB2301DFF5E7537B5A7000A65BC5540 at SN2PR03MB2301.namprd03.prod.outlook.com>
>> 	
>> Content-Type: text/plain; charset="us-ascii"
>>
>> How long are your simulations? I build a DPPC bilayer with charmm-GUI and simulate for 300 ns at 323 K and the APL has a mean of 0.61 nm^2 and a standard deviation of 0.01 nm^2. However, the APL does happen to dip down to 0.59 within 10 ns... it's just that the fluctuations will also sometimes take it as high as 0.65 and as low as 0.57. Maybe give us your simulation time and upload a plot of APL vs. time and post the link here (no direct attachments please). If you're running 10-20 ns and you see the APL get low then you may simply need to run for longer.
>>
>> Here is the data from my simulation of DPPC at 323K:
>> https://www.dropbox.com/s/adu4ft8dhuyc9c2/dppc_323k_apl.pdf?dl=0
>>
>> I suggest you figure things out with DPPC before moving on to your PA lipids.
>>
>> Chris.
>>
>> ________________________________________
>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se <gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of Nidhin Thomas <nidhin.thomas0624 at gmail.com>
>> Sent: 13 June 2016 19:32:47
>> To: gromacs.org_gmx-users at maillist.sys.kth.se
>> Subject: [gmx-users] Decreased Area/Lipid of Lipid Bilayer from CHARMM-GUI
>>
>> Hello everyone,
>>
>> I have also given below the map file that I have used for equilibration.
>>
>> integrator = md
>> dt = 0.002
>> nsteps = 2000000
>> nstlog = 1000
>> nstxout = 5000
>> nstvout = 1000
>> nstfout = 1000
>> nstcalcenergy = 100
>> nstxtcout       = 1000
>> nstenergy = 1000
>> ;
>> cutoff-scheme = Verlet
>> nstlist = 20
>> rlist = 1.2
>> coulombtype = pme
>> rcoulomb = 1.2
>> vdwtype = Cut-off
>> vdw-modifier = Force-switch
>> rvdw_switch = 1.0
>> rvdw = 1.2
>> ;
>> tcoupl = Nose-Hoover
>> tc_grps = MEMB SOL_ION
>> tau_t = 1.0 1.0
>> ref_t = 323.15 323.15
>> ;
>> pcoupl = Parrinello-Rahman
>> pcoupltype = semiisotropic
>> tau_p = 5.0
>> compressibility = 4.5e-5 4.5e-5
>> ref_p = 1.0 1.0
>> ;
>> constraints = h-bonds
>> constraint_algorithm = LINCS
>> continuation = yes
>> ;
>> nstcomm = 100
>> comm_mode = linear
>> comm_grps = MEMB SOL_ION
>> ;
>> refcoord_scaling = com
>>
>>
>> Thanks,
>>
>> Nidhin Thomas
>> University of Houston
>>
>>> Message: 4
>>> Date: Mon, 13 Jun 2016 17:51:43 +0000
>>> From: Christopher Neale <chris.neale at alum.utoronto.ca>
>>> To: "gromacs.org_gmx-users at maillist.sys.kth.se"
>>>      <gromacs.org_gmx-users at maillist.sys.kth.se>, "gmx-users at gromacs.org"
>>>      <gmx-users at gromacs.org>
>>> Subject: Re: [gmx-users] Decreased Area Per Lipid for Lipid Bilayer
>>>      obtained        from CHARMM-GUI
>>> Message-ID:
>>>      <SN2PR03MB23010A1EA13D95F4EC7877C1C5530 at SN2PR03MB2301.namprd03.prod.outlook.com>
>>>
>>> Content-Type: text/plain; charset="Windows-1252"
>>>
>>> In future posts, it is best to copy and paste your .mdp file because we can not all get attachments from the list.
>>>
>>> Regarding your results, it is my understanding that the CHARMM-GUI has parameters for, and can build, many lipids systems whose parameters have not been completely validated by simulations in the literature (e.g. for things like APL). Last time I looked, PG was the only anionic charmm36 lipid that was shown to behave properly in bilayers (Klauda), though others may have since been shown to work well.
>>>
>>> If the issue is not simply that the PA parameters are not very good, then one likely source of problem is that perhaps you are not using the NBfix ions? That could be a big deal. I never use Na with membranes for this reason, so you could try KCl instead.
>>>
>>> Chris.
>>>
>>> ________________________________________
>>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se <gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of Nidhin Thomas <nidhin.thomas0624 at gmail.com>
>>> Sent: 12 June 2016 18:38:43
>>> To: gromacs.org_gmx-users at maillist.sys.kth.se
>>> Subject: [gmx-users] Decreased Area Per Lipid for Lipid Bilayer obtained        from CHARMM-GUI
>>>
>>> Hello GROMACS Users,
>>>
>>> I have modelled a mixed bilayer system consisting of 35 DPPC lipids and one POPA lipid (in each monolayers) using CHARMM-GUI. NPT ensemble was chosen while creating the model. TIP3 water model was used for modeling. I did not use surface tension for the membrane.
>>>
>>> I have simulated the system for 50 nanoseconds now. I have noticed that average area per lipid of the system is only 58.55 Angstrom2. I saw from literature that it should be around 63 and even at CHARMM-GUI, it is mentioned as 63 while creating the bilayer.
>>>
>>> I have used the exact .mdp files given by CHARMM-GUI for minimization, equilibration and production run.
>>>
>>> Can anyone please help me identify what could have possibly gone wrong in my simulation? I have attached the .mdp file used for production run and equilibration here for reference.
>>>
>>> In addition, I keep on getting these NOTES while running the grompp command prior to mdrun before it creates a .tpr file. I don?t know if this has got something to do with the simulation.
>>>
>>> NOTE 1 [file step7_production_2.mdp]:
>>> leapfrog does not yet support Nose-Hoover chains, nhchainlength reset to 1
>>>
>>> Estimate for the relative computational load of the PME mesh part: 0.05
>>> Excluding 2 bonded neighbours molecule type 'TIP3'
>>>
>>> There was 1 note
>>> Excluding 1 bonded neighbours molecule type 'POT'
>>> Removing all charge groups because cutoff-scheme=Verlet
>>> Setting the LD random seed to 2417118902
>>> Estimate for the relative computational load of the PME mesh part: 0.05
>>>
>>> There was 1 note
>>> Removing all charge groups because cutoff-scheme=Verlet
>>>
>>> Thanks a lot for the help!
>>>
>>> Nidhin Thomas
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>> -----------------------------

-- 
==================================================

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

==================================================