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

Ebert Maximilian m.ebert at umontreal.ca
Fri May 29 20:53:13 CEST 2015


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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