[gmx-users] Re: Gromacs 54a7 force field

[Thomas Piggot]

Hi,

Justin, I am interested by your comments regarding the CHARMM lipids. In 
particular can you elaborate as to why you think that the CHARMM lipids 
are better than the united-atom ones (such as Berger and several GROMOS 
variants).

As for the original question, the modifications in going from GROMOS 
53A6 to 54A7 will not influence the combination with the Berger lipid 
parameters, if the most common approach of using the parameters from the 
'lipid.itp' file is taken. The interactions between protein and lipid 
will remain the same, with the van der Waals interactions between the 
protein and lipid treated using the GROMOS87 parameters as defined in 
lipid.itp. From my experiences I would strongly recommend using 54A7 
over 53A6, as we have seen instability in short helices in 53A6 that is 
not reproduced when simulating the same systems with several other force 
fields.

For the 'best' force field to choose when simulating a membrane-protein 
system, there is no definitive answer that I (or anyone else) can give 
you (yet). My own opinion is that currently CHARMM36 is probably too 
slow (given that I would strongly recommend the use of the CHARMM TIP3P 
water model with this force field) and that the all-atom protein force 
fields are probably better than the united-atom ones. This means that I 
would (for a PC membrane) use Berger for the lipids with OPLS-AA/L or an 
AMBER force field for the protein. This is just my (current) opinion 
though, I strongly suggest doing lots of your own reading before making 
your mind up.

Cheers

Tom

On 18/07/12 22:55, Justin Lemkul wrote:
>
>
> On 7/18/12 5:51 PM, Rajat Desikan wrote:
>> "54A7 also introduced changes to the Gromos96 lipid parameters"
>> How will this change my inclusion of the berger lipid parameters? Any 
>> thing
>> that I should pay special attention to? Are there other lipid parameters
>> more compatible?
>
> There are better force fields for lipids, but they require the use of 
> CHARMM. There may be other suitable united atom force fields. My 
> comment was intentionally generic; I don't know how well 54A7 pairs 
> with the Berger parameters.  In theory, it should be fine, but since 
> Gromos96 parameters for lipids have been tweaked, maybe the balance of 
> forces in the parameters for proteins and lipids will be affected.  
> There was a new lipid atom type introduced to make Gromos96 lipids 
> better.  They're still not as good as CHARMM, though.
>
>> I heard from a faculty member at our Institute that the 53a6 is a bad 
>> ff for
>> a protein with a lot of alpha helices for longer simulations. She 
>> apparently
>> saw the helices unravel when they were supposed to be stable.
>>
>
> This is a hot topic.  Conventional wisdom does demonstrate that 53A6 
> destabilizes helices, but others will contend that 53A6 is perfectly 
> suitable for reproducing many experimental observables, including NMR 
> signals.  I tend to think that there is some bias, but all force 
> fields have shortcomings.  54A7 is certainly better in terms of 
> helical stabilization, from what I can see.
>
> -Justin
>

-- 
Dr Thomas Piggot
University of Southampton, UK.