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

[Sim gmx]

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/gmane.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!
>