[gmx-users] Lipid parameters for GROMOS96 force fields

[Tsjerk Wassenaar]

Hi,

Well, we have compared the G53a5/6 force field with the 43a2 one and
found consistently larger radii of gyration and higher RMSDs,
suggesting decreased stability. There's a thorough account of it in my
thesis (http://dissertations.ub.rug.nl/FILES/faculties/science/2006/t.a.wassenaar/04emb_c4.pdf)
and it's been published in JPCB in 2007 (DOI: 10.1021/jp068580v).

Cheers,

Tsjerk

On Thu, Jan 21, 2010 at 2:24 PM, XAvier Periole <x.periole at rug.nl> wrote:
>
> The instability of helices with the G53a6 force field is definitely real
> and unfortunately not documented. Some people are working on it ...
>
> I would advise to be very carefull in interpreting results with this FF.
>
> XAvier.
>
> On Jan 21, 2010, at 2:13 PM, Justin A. Lemkul wrote:
>
>>
>>
>> Krzysztof Mlynarczyk wrote:
>>>
>>> 2010/1/21 Justin A. Lemkul <jalemkul at vt.edu <mailto:jalemkul at vt.edu>>
>>>   Krzysztof Mlynarczyk wrote:
>>>       2. If not, is there any way to derive the proper parameters for
>>>       the force field of my choice using the lipid parameters from
>>>       Peter Tieleman's website or e.g. the parameters published by
>>>       Andreas Kukol for G53a6?
>>>   I don't see why you need to do such reverse engineering.  The Kukol
>>>   parameters for lipids under 53a6 can be directly combined with a
>>>   G53a6 protein without any issues; I believe that was the purpose of
>>>   the whole new derivation :)
>>> I received a message that G53a6 is beta-sheet biased and alpha helices do
>>> not perform as well as they should. My protein contains 7 transmembrane
>>> helices, that's why I'm worried.
>>
>> Is this published somewhere?  That would be important information.
>>  Perhaps this is the case for model peptides or short fragments, but I have
>> certainly done a number of simulations using 53a6 with well-folded globular
>> proteins and I do not see any such instability (i.e., alpha->beta conversion
>> or unwinding of alpha-helices).  I do believe it is possible in certain
>> scenarios, but I don't know that a large 7TM protein like yours would suffer
>> adversely.
>>
>>> I know that there are changes between parameter sets both in non-bonded
>>> and bonded terms and one rtp entry will probably not work well when pasted
>>> into a different force field from the same family. G96 family uses symbols
>>> like gd_5 that are substituted by appropriate parameters later through the
>>> use of preprocessor. While it is possible to find that gd_5 is the same as
>>> gd_15 in another version of G96 and substitute those symbols in topologies,
>>> the changes in non bonded parameters still can spoil what was working well
>>> elsewhere. That's why I was also asking for some checked and ready-to-use
>>> topologies for a particular force field.
>>
>> Many of the bonded parameters carry over between force fields, but
>> certainly new entries were created between 43a2 and 53a6, so yes, some
>> re-working would likely be necessary.  There is a lipid 43a2 parameter set
>> on the User Contribution site, like I said before, I just don't know if
>> there is a reference for it.
>>
>>>   As an aside, you are quite right that multiple force fields within
>>>   the same simulation is incorrect.  However, the Berger lipid
>>>   parameters may be an exception to this rule, since they are really a
>>>   hybridized version of OPLS-UA and Gromos87 parameters (some of which
>>>   were modified anyway), so they really don't belong to any one
>>>   particular force field.  The Berger/G87 combination is widely used,
>>>   but essentially amounts to the following: lipid interactions are
>>>   Berger-Berger or OPLS-OPLS interactions, while protein-lipid
>>>   interations are Berger-G87, and protein-protein interactions are
>>>   G87-G87.  You can see quite quickly why things become complicated!
>>>   Based on a discussion I had with Dr. Tieleman, it seems to be
>>>   reasonable to use the G96 parameter set of your choice in
>>>   conjunction with lipid.itp (Berger lipids), although other
>>>   approaches may be more rigorously correct (pure G96 parameters such
>>>   as those by Kukol, pure OPLS recently derived by Ulmschneider, or
>>>   the modifications to the Berger parameters from the Tieleman group,
>>>   to name a few).  If you want to use a G96-lipid.itp combination, I
>>>   created a tutorial that teaches you how to build the system and
>>>   properly prepare the topology.  It is linked from the Tutorials page
>>>   of the Gromacs site.
>>> I found this tutorial earlier and was also in doubt if this approach was
>>> correct. But if it works, perhaps I should give it a try.
>>> I gotta make a _good_ decision in the end...
>>
>> As do we all :)  My work with G53a6+Berger has thus far been quite
>> reliable, from everything I can measure, but that certainly does not
>> preclude the possibility (even likelihood) that there are better procedures
>> out there, like those I quoted above, and certainly others (CHARMM is also
>> popular for membrane proteins, but Gromacs will only *officially* support
>> CHARMM as of version 4.1).
>>
>> -Justin
>>
>>> Christopher
>>
>> --
>> ========================================
>>
>> Justin A. Lemkul
>> Ph.D. Candidate
>> ICTAS Doctoral Scholar
>> MILES-IGERT Trainee
>> Department of Biochemistry
>> Virginia Tech
>> Blacksburg, VA
>> jalemkul[at]vt.edu | (540) 231-9080
>> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>>
>> ========================================
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-- 
Tsjerk A. Wassenaar, Ph.D.

Computational Chemist
Medicinal Chemist
Neuropharmacologist