[gmx-users] How to use Höltje's cholesterol parameters ?

[Sim gmx]

Anyone ?
Do you think it does not deserve any attention given the similiraties
between GROMOS87 and GROMOS96 FF ?

2016-12-12 9:38 GMT+01:00 Sim gmx <simgmx at gmail.com>:

> Please, could someone help me with that ? Are my questions unclear ?
>
> 2016-12-09 9:48 GMT+01:00 Sim gmx <simgmx at gmail.com>:
>
>> Hello everyone,
>>
>> I am currently working on interactions between small biomolecules and
>> bilayers. Phospholipids parameters come from Peter Tieleman's website
>> (Berger lipids forcefield) and the small compounds are parametrized for
>> gromos53a6. I would like to add cholesterol to my bilayers, which is very
>> frequently done with Höltje cholesterol parameters (see e.g.
>> http://pubs.acs.org/doi/full/10.1021/ja211929h ). However, these Höltje
>> parameters were originally designed for the ffgmx forcefield, which is
>> quite old.
>>
>> The way we should include these parameters in a Berger lipids -
>> gromos53a6 mixed forcefield has already raised some questions on the
>> mailing list: http://comments.gmane.org/gman
>> e.science.biology.gromacs.user/68478
>>
>> However, it remains unclear to me. I guess we can use the bonded
>> parameters as they are written in the original topology from Höltje, but it
>> becomes more complicated when talking about the non bonded interactions.
>> Every atomtypes but two (CB and CR61) from ffgmx also exist in gromos53a6
>> (and are thus included in the gromos53a6 forcefield). Hence, I think there
>> are 3 possible ways to make a simulation run without crashing when
>> including this cholesterol to a berger lipid - gromos53a6 forcefield:
>>
>> 1) Keeping the cholesterol topology file unchanged, and adding the
>> atomtypes 'CB' and 'CR61' to the forcefield file 'ffnonbonded.itp', with
>> their parameters coming from the ffgmx forcefield. It means that each
>> cholesterol will be seen as a "hybrid object", with most of the atomtypes
>> being gromos53a6 ones, and CB and CR61 being ffgmx atomtypes. Non bonded
>> interaction involving CB or CR61 atomtypes will be computed with the
>> standard combination rule.
>>
>> 2) Keeping the Berger lipid - gromos53a6 forcefield unchanged, and
>> changing the atomtype 'CB' to 'C' and the atomtype 'CR61' to 'CR1' into the
>> cholesterol topology file, C and CR1 being the corresponding atomtypes
>> found in gromos53a6. It means that each cholesterol will be seen as a
>> "gromos53a6" object for the non bonded interactions.
>>
>> 3) Changing every atomtype from the cholesterol topology file to make
>> them different from gromos53a6 atomtypes (for instance: CH2 becomes CH2F
>> (for ffgmx)) and adding all these ffgmx specific atomtypes in the
>> forcefield file 'ffnonbonded.itp' with the proper parameters. It means that
>> each cholesterol will be seen as a "ffgmx object", each non bonded
>> interaction being computed with the standard combination rule.
>>
>> Solution 1 seems to be quite obvious, but it sounds a bit weird to me,
>> because it mixes up ffgmx and 53a6 interactions. Solution 2 seems more
>> consistent, but if we use "pure" gromos53a6 non bonded interactions, maybe
>> we should also "translate" bonded parameters from ffgmx to gromos53a6 ?
>> Solution 3 is maybe the most logical solution, but it seems that ffgmx is
>> now considered to be deprecated...
>>
>> The question becomes even more complicated when considering the fact that
>> CH2 and CH3 atomtypes could lead to overcondensed bilayers, according to
>> some authors who advise to switch them to 'LP2' and 'LP3' Berger lipid
>> atomtypes.
>>
>> It is possible that those solutions give quite similar results (if ffgmx
>> and gromos53a6 forcefields are "similar enough"), but I am very curious to
>> know the 'usual' protocol that is followed when people only write "Höltje
>> parameters were used".
>>
>> Another solution would be to use the cholesterol topology file found on
>> ATB (manual validation), frequently used by Pr. Alan E. Mark, but never
>> used with Berger lipids phospholipids...
>>
>> Thank you in advance for your help!
>>
>
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