[gmx-users] Water organic solvents mixtures: Which force field to use and best practice to derive parameters

Alan alanwilter at gmail.com
Sat May 30 09:34:18 CEST 2015


Hi

Not because I developed ACPYPE, but if I’d like to be the most rigorous as
possible, I’d go with ACPYPE and RED (http://q4md-forcefieldtools.org/).

Alan

On 29 May 2015 at 20:53, Ebert Maximilian <m.ebert at umontreal.ca> wrote:

> I continued to define good partial charges using the tools suggested. I
> found that the combination of Maestro + ffconv or mktop, ACPYPE and
> antechamber + mktop have all advantages and disadvantages depending on the
> organic molecule.
>
> for instance for acetone with maestro and mktop i could achieve the same
> topology as virtual chemistry. I next tried to generate a topology for
> iso-propanol. Here ACPYPE charges with the mktop atom types gave the closes
> density to the experimental one. I also tried to calculate the heat
> capacity with Cp and Cv to compare it with the literature. My box is
> 2.3x2.3x2.3nm large and has about 150 molecules of the organic solvent.
> After 1ns of NPT i get values which are 5x higher than the literature value
> (gmx energy -f npt.edr -fluct_props -nmol 100). I also tried a box 5x5x5nm
> with over 1000 molecules and got the same result. Any idea why the
> simulation using OPLS AA FF is so far of when it comes to the heat capacity?
>
> thanks
> max
>
>
>
> > On May 28, 2015, at 9:19 AM, Ebert Maximilian <m.ebert at umontreal.ca>
> wrote:
> >
> > Thanks Justin and Kalev this brings me already much further. I tried
> ffld_server and it works just fine. However, it is like a black box. I
> can’t really find the documentation on how ffld_server gets the charges. Do
> you know where to find the documentation?
> >
> > Thanks
> >
> >> On May 28, 2015, at 2:22 AM, Kalev Takkis <kalev.takkis at gmail.com>
> wrote:
> >>
> >> If you're after OPLS topologies for GROMACS then one way to derive them
> is
> >> via Schrödinger's Maestro (free academics version is sufficient) and
> >> Andrey Frolov's
> >> ffconv script (http://frolov-pchem.wikispaces.com/ffconv.py). You can
> >> create a force field represesentation of a molecule with the former
> >> (described here http://www.schrodinger.com/kb/809) and then convert it
> to
> >> GROMACS format with the latter.
> >>
> >> All the best,
> >> Kalev
> >>
> >> On 28 May 2015 at 03:37, Mohd Farid Ismail <
> mohd.farid.ismail at yandex.com>
> >> wrote:
> >>
> >>> You can try R.E.D. Server.  It has more charge models (I don't know
> >>> whether that will help).
> >>>
> >>> Also, IMO, one should target the density and the static dielectric
> >>> constant when it comes to VDW and partial charges.  I saw a recent
> paper
> >>> that might be of interest to you
> >>> http://pubs.acs.org/doi/abs/10.1021/jp3002383
> >>>
> >>> --
> >>> Mohd Farid Ismail
> >>>
> >>>
> >>>
> >>>
> >>> 28.05.2015, 05:13, "Ebert Maximilian" <m.ebert at umontreal.ca>:
> >>>
> >>> I just finished a 1 ns NPT calculation of a 2.3x2.3x2.3 nm box filled
> with
> >>> acetone (130 molecules). The expected density at 300K is 784.1 kg/m^3.
> For
> >>> the virtual chemistry parameters i calculated 798.6 (close to the
> 800.1±0.2
> >>> value on their website) and for the parameter derived as explain in
> >>> previous mail I got 817.0 which seems too high. Does anybody has an
> advice
> >>> how I could improve the derivation of my parameters?
> >>>
> >>> Thank you very much,
> >>>
> >>> max
> >>>
> >>> On May 27, 2015, at 3:25 PM, Ebert Maximilian <m.ebert at umontreal.ca>
> >>> wrote:
> >>>
> >>> I read more about organic solvents in MD and came to the conclusion
> that
> >>> OPLS is indeed the best way to go. Since I couldn’t really find an
> >>> accessible tutorial how to derive topology files for GROMACS and the FF
> >>> OPLS/AA I will document my progress here. Maybe this is of help for
> >>> somebody in the future. In addition, I would like to ask the community
> to
> >>> help me in case you see problems with my approach. Once I have a good
> >>> protocol I will write a tutorial and make it available online.
> >>>
> >>> To validate my approach I am trying to create a parameter set for
> acetone
> >>> which I found on  http://virtualchemistry.org. To generate the OPLS
> >>> topology I used a tool suggested by many people called mktop in version
> >>> 2.2.1. I downloaded the ideal geometry of acetone from Ligand Expo and
> >>> generated a GROMACS topology file using the following command:
> >>>
> >>> mktop_2.2.1.pl -i ACN_ideal.pdb -o acn_topology.top -ff opls -conect
> yes
> >>>
> >>> In order to get the charges for this organic molecule I downloaded the
> >>> most recent amber tools and compiled it. I used the AM1-BCC charge
> model to
> >>> generate charges for acetone using the following instructions in
> >>> antechamber:
> >>>
> >>> antechamber -i ACN_ideal.pdb -fi pdb -o acn.mol2 -fo mol2 -c bcc -s 2
> >>>
> >>> I opened the resulting mol2 file in Chimera to map the atoms to the
> atoms
> >>> in my .top file. The charges calculated by antechamber look reasonable
> and
> >>> are comparable to the validated OPLS topology from virtual chemistry:
> >>>
> >>> virtual chemistry charges
> >>>
> >>> [ atoms ]
> >>> ;   nr       type  resnr residue  atom   cgnr     charge       mass
> >>> typeB    chargeB      massB
> >>>        1  opls_280         1       LIG         C         1      0.47
> >>>  12.011
> >>>        2  opls_135         1       LIG         C         2     -0.18
> >>>  12.011
> >>>        3  opls_135         1       LIG         C         3     -0.18
> >>>  12.011
> >>>        4  opls_281         1       LIG         O         4     -0.47
> >>> 15.9994
> >>>        5  opls_282         1       LIG         H         5      0.06
> >>>   1.008
> >>>        6  opls_282         1       LIG         H         6      0.06
> >>>   1.008
> >>>        7  opls_282         1       LIG         H         7      0.06
> >>>   1.008
> >>>        8  opls_282         1       LIG         H         8      0.06
> >>>   1.008
> >>>        9  opls_282         1       LIG         H         9      0.06
> >>>   1.008
> >>>       10  opls_282         1       LIG         H        10      0.06
> >>>   1.008
> >>>
> >>>
> >>> antechamber AM1-BCC derived
> >>>
> >>> [ atoms ]
> >>> ;   nr       type  resnr residue  atom   cgnr     charge       mass
> >>> typeB    chargeB      massB
> >>>       1  opls_280   1   ACN      C1    1    0.56     12.011
> >>>       2  opls_281   1   ACN      O1    1   -0.52     15.9994
> >>>       3  opls_135   1   ACN      C2    2   -0.20     12.011
> >>>       4  opls_135   1   ACN      C3    3   -0.20     12.011
> >>>       5  opls_282   1   ACN      H1    2    0.06     1.008
> >>>       6  opls_282   1   ACN      H2    2    0.06     1.008
> >>>       7  opls_282   1   ACN      H3    2    0.06     1.008
> >>>       8  opls_282   1   ACN      H4    3    0.06     1.008
> >>>       9  opls_282   1   ACN      H5    3    0.06     1.008
> >>>      10  opls_282   1   ACN      H6    3    0.06     1.008
> >>>
> >>> The atom types were guessed correctly by mktop and also the charge
> groups
> >>> make sense I think. So far so good.
> >>>
> >>> I realize some differences between the two topologies. First the mktop
> >>> topology also includes FF constants for the different bonds and angles:
> >>>
> >>> [ bonds ]
> >>> 1 2 1   0.121  476976.0
> >>> 1 3 1   0.151  265265.6
> >>> 1 4 1   0.151  265265.6
> >>> 3 5 1   0.109  284512.0
> >>> 3 6 1   0.109  284512.0
> >>> 3 7 1   0.109  284512.0
> >>> 4 8 1   0.109  284512.0
> >>> 4 9 1   0.109  284512.0
> >>> 4 10 1   0.109  284512.0
> >>>
> >>>
> >>> [ angles ]
> >>> 1 3 5 1  109.460  292.880
> >>> 1 3 6 1  109.473  292.880
> >>> 1 3 7 1  109.484  292.880
> >>> 1 4 8 1  109.466  292.880
> >>> 1 4 9 1  109.435  292.880
> >>> 1 4 10 1  109.477  292.880
> >>> 2 1 3 1  119.985  669.440
> >>> 2 1 4 1  119.985  669.440
> >>> 3 1 4 1  120.029  585.760
> >>> 5 3 6 1  109.445  276.144
> >>> 5 3 7 1  109.464  276.144
> >>> 6 3 7 1  109.502  276.144
> >>> 8 4 9 1  109.483  276.144
> >>> 8 4 10 1  109.504  276.144
> >>> 9 4 10 1  109.462  276.144
> >>>
> >>> compared to the virtual chemistry file:
> >>>
> >>> [ bonds ]
> >>> ;  ai    aj funct            c0            c1            c2
> c3
> >>>   1     2     1
> >>>   1     3     1
> >>>   1     4     1
> >>>   2     5     1
> >>>   2     6     1
> >>>   2     7     1
> >>>   3     8     1
> >>>   3     9     1
> >>>   3    10     1
> >>>
> >>> [ angles ]
> >>> ;  ai    aj    ak funct            c0            c1            c2
> >>>          c3
> >>>   2     1     3     1
> >>>   2     1     4     1
> >>>   3     1     4     1
> >>>   1     2     5     1
> >>>   1     2     6     1
> >>>   1     2     7     1
> >>>   5     2     6     1
> >>>   5     2     7     1
> >>>   6     2     7     1
> >>>   1     3     8     1
> >>>   1     3     9     1
> >>>   1     3    10     1
> >>>   8     3     9     1
> >>>   8     3    10     1
> >>>   9     3    10     1
> >>>
> >>>
> >>> Should I trust the mktop parameters or delete them? To look if my
> >>> parameters are correct I did a short MD with a box containing only
> acetone
> >>> based on the two topologies. The MD is still running but I wanted to
> >>> compare the density and see how it matches with reality.
> >>>
> >>> What do you think about this approach? What would have been a better
> way?
> >>> How can I make sure that the charges are correct?
> >>>
> >>> Thanks for your input.
> >>>
> >>> Max
> >>>
> >>>
> >>>
> >>> On May 27, 2015, at 11:54 AM, Ebert Maximilian <m.ebert at umontreal.ca
> >>> <mailto:m.ebert at umontreal.ca>> wrote:
> >>>
> >>> Hi there,
> >>>
> >>> I am about to setup a water:organic solvent mixture with a protein. I
> >>> found many organic molecules on http://virtualchemistry.org with
> >>> definitions for the OPLS FF. However, some are missing so I would need
> to
> >>> derive the parameters myself. Before going into more details I was
> >>> wondering if OPLS is to be preferred if organic solvent is present or
> can
> >>> AMBER also be used? It seems that using ACPYPE with AMBER is much more
> >>> accessible than using any other method to derive the parameters for
> organic
> >>> molecules.
> >>>
> >>> Thanks for your advice.
> >>> --
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-- 
Alan Wilter SOUSA da SILVA, DSc
Bioinformatician, UniProt
European Bioinformatics Institute (EMBL-EBI)
European Molecular Biology Laboratory
Wellcome Trust Genome Campus
Hinxton
Cambridge CB10 1SD
United Kingdom
Tel: +44 (0)1223 494588


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