[gmx-users] Force Field for Bilayer Simulations with Cholesterol and Proteins

Fri May 9 15:56:38 CEST 2014

Hello,

I appreciate all the responses.

I would like to keep my simulations United Atom. And the paper I am basing
my work and parameter files on used ffgmx with the Holtje cholesterol and
Berger parameters for the lipids. Therefore, most of the interactions are
Berger interactions, except for the Berger-Gromos interactions of lipid to
cholesterol. I now have learned that a modified cholesterol with Berger
parameters might be better and would reduce effects of overcondensation.

I plan on testing 53a6 with Berger lipid parameters and modified
cholesterol (with Berger LP2 and LP3 replacing CH2 and CH3) to see if it
has any significant qualitative effects on my results for a protein-free
bilayer. This would be especially important if I want to compare these
results with a protein-containing bilayer, since I've come to realize the
gmx force field is not the best for proteins.

-David

On Fri, May 9, 2014 at 8:02 AM, David van der Spoel <spoel at xray.bmc.uu.se>wrote:

> On 2014-05-09 13:47, Piggot T. wrote:
>
>> Hi David,
>>
>> Firstly I would say, is there any reason why you need to use the
>> Berger/Höltje/GROMOS force field combination? There are several other
>> options available that I can think of which may be easier/better for you.
>> You could use the Slipids (with an AMBER force field for the protein),
>> CHARMM36 for all of the components of your system, or if you do want to
>> stick with a united-atom force field, you could still use one of the GROMOS
>> force fields ((e.g. 54A7) with the GROMOS-CKP lipids and the consistent
>> cholesterol parameters that you can download from the manual entry of the
>> automated topology builder. I haven't ever simulated cholesterol so I
>> cannot really recommend which may be better than others for this molecule,
>> but there will be plenty of literature out there to look at regarding this.
>>
>> Secondly, if you do want to stay with the Berger/Höltje/GROMOS
>> combination, you could probably add the missing atomtypes to the GROMOS
>> force field you wish to use. I would strongly advise against using the old
>> 'ffgmx' force field, this has been shown to behave pretty poorly for
>> proteins. Do be careful in doing this addition of atomtypes, as the GROMOS
>> force fields are different from the all-atom force fields in as much as the
>> atomtypes have multiple van der Waals interaction parameters used for
>> interactions with different atomtypes. Some of the GROMOS papers describe
>> this in far more detail.
>>
>> Just some of my thoughts, hopefully of some use!
>>
>>
> You could also look here:
>
> http://cmb.bio.uni-goettingen.de/downloads.html
>
>
>  Cheers
>>
>> Tom
>> --
>> Dr Thomas Piggot
>> University of Southampton, UK.
>>
>>
>> ________________________________________
>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se [
>> gromacs.org_gmx-users-bounces at maillist.sys.kth.se] on behalf of Ollila
>> Samuli [samuli.ollila at aalto.fi]
>> Sent: 09 May 2014 11:42
>> To: gmx-users at gromacs.org
>> Subject: Re: [gmx-users] Force Field for Bilayer Simulations with
>> Cholesterol and Proteins
>>
>> Hi,
>>
>> I used ffgmx.itp. It contains CB.
>>
>> BR,
>> Samuli Ollila
>>
>> ________________________________________
>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se [
>> gromacs.org_gmx-users-bounces at maillist.sys.kth.se] on behalf of David
>> Ackerman [da294 at cornell.edu]
>> Sent: Wednesday, May 07, 2014 10:30 PM
>> To: Discussion list for GROMACS users
>> Subject: Re: [gmx-users] Force Field for Bilayer Simulations with
>> Cholesterol and Proteins
>>
>> Thank you for your advice.
>>
>> Which force field was used? I have downloaded the cholesterol parameters
>> from Höltje et al, but atomtypes like CB do not exist in the force field I
>> am using (53a6). Did you change these to other atomtypes as well, or were
>> you using a force field that included them?
>>
>> -David
>>
>>
>> On Wed, May 7, 2014 at 8:59 AM, Ollila Samuli <samuli.ollila at aalto.fi
>> >wrote:
>>
>>  Hi,
>>>
>>> In my understanding the CH2-LP2 attraction is stronger than LP2-LP2
>>> attraction in the Berger/Höltje combination you described. If you then
>>> have
>>> CH2 groups in cholesterol and LP2 groups in lipids, it might lead to too
>>> condensed bilayer. I think that the related issue is discussed here:
>>>
>>> http://dx.doi.org/10.1088/0953-8984/18/28/S07
>>>
>>> and here:
>>>
>>> http://dx.doi.org/10.1039/C2CP42738A
>>>
>>> we have changed the CH2 groups in cholesterol to LP2 groups and compared
>>> the results quite extensively to the NMR measurements.
>>>
>>> BR,
>>> Samuli Ollila
>>>
>>>
>>> ________________________________________
>>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se [
>>> gromacs.org_gmx-users-bounces at maillist.sys.kth.se] on behalf of David
>>> Ackerman [da294 at cornell.edu]
>>> Sent: Monday, May 05, 2014 7:39 AM
>>> To: gromacs.org_gmx-users at maillist.sys.kth.se
>>> Subject: [gmx-users] Force Field for Bilayer Simulations with Cholesterol
>>>        and Proteins
>>>
>>> Hello,
>>>
>>> I have been performing simulations of multi-component bilayers using
>>> parameters described in the following paper:
>>> http://www.ncbi.nlm.nih.gov/pubmed/23470157. They use the ffgmx
>>> forcefield
>>> with Berger lipid parameters included. They also use cholesterol from
>>> Holtje et. al (
>>> http://www.sciencedirect.com/science/article/pii/S000527360100270X),
>>> which
>>> was parameterized for the ffgmx force field.
>>>
>>> I noticed that unlike the KALP-15 GROMACS tutorial which suggests
>>> deleting
>>> the default lipid-gromos Berger interactions, the authors kept those
>>> interactions in the force field. In light of newer force fields, are
>>> these
>>> older force fields wither Berger parameters still acceptable? The
>>> cholesterol model seems commonly used, so I am unsure how to use
>>> cholesterol with a newer force field.
>>>
>>> Furthermore, if I were to include proteins in the simulation, would I
>>> still
>>> be able to use the same ffgmx force field with Berger parameters
>>> (including
>>> lipid-gromos interactions)?
>>>
>>> Thank you,
>>> David
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>
> --
> David van der Spoel, Ph.D., Professor of Biology
> Dept. of Cell & Molec. Biol., Uppsala University.
> Box 596, 75124 Uppsala, Sweden. Phone:  +46184714205.
> spoel at xray.bmc.uu.se    http://folding.bmc.uu.se
>
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