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

Ebert Maximilian m.ebert at umontreal.ca
Mon Jun 1 18:02:58 CEST 2015


Hi,

thanks diana for your input and for the review. I never used GROMOS so far and I feel less comfortable using an unknown FF at this point. I am writing a tutorial on how to parameterize organic molecules right now and will publish it this week. Maybe you can comment on the strategy to have a relatively clean and broad approach. I was wondering which physical-chemical properties did you use to verify your definition? So far I am looking at density, Cp and Cv.

Thanks!

Max

> On May 28, 2015, at 5:15 AM, Diana Lousa <dlousa at itqb.unl.pt> wrote:
> 
> Hi,
> 
> Our group has done many studies using enzymes in organic solvents (with
> different amounts of water) and we always used the GROMOS FF for the
> proteins and compatible  parameters for the solvents. We can find a review
> of enzyme simulations in nonaqueous solvents here:
> http://pubs.rsc.org/en/Content/ArticleLanding/2013/CP/c3cp51761f#!divAbstract
> 
> 
> The parameters that we used for different solvents were able to reproduce
> their physical-chemical properties. I can also tell you that from our
> experience the latest GROMOS FF are able to reproduce the structural
> properties of small peptides and proteins also seem to be quite stable when
> these FF are used. Thus, using GROMOS 54A7 for the protein and compatible
> parameters for organic solvents can be a good choice. However, if you want
> to use PME for long-range electrostatics, you have to test if these
> parameters work in these conditions, because they were developed to be used
> with RF.
> 
> 
> On Thu, May 28, 2015 at 7:22 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.
>>> --
>>> Gromacs Users mailing list
>>> 
>>> * Please search the archive at
>>> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before
>>> posting!
>>> 
>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>> 
>>> * For (un)subscribe requests visit
>>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>>> send a mail to gmx-users-request at gromacs.org<mailto:
>>> gmx-users-request at gromacs.org>.
>>> 
>>> --
>>> Gromacs Users mailing list
>>> 
>>> * Please search the archive at
>>> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before
>>> posting!
>>> 
>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>> 
>>> * For (un)subscribe requests visit
>>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>>> send a mail to gmx-users-request at gromacs.org.
>>> 
>>> --
>>> Gromacs Users mailing list
>>> 
>>> * Please search the archive at
>>> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before
>>> posting!
>>> 
>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>> 
>>> * For (un)subscribe requests visit
>>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>>> send a mail to gmx-users-request at gromacs.org.
>>> 
>>> 
>>> --
>>> Gromacs Users mailing list
>>> 
>>> * Please search the archive at
>>> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before
>>> posting!
>>> 
>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>> 
>>> * For (un)subscribe requests visit
>>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>>> send a mail to gmx-users-request at gromacs.org.
>>> 
>> --
>> Gromacs Users mailing list
>> 
>> * Please search the archive at
>> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before
>> posting!
>> 
>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>> 
>> * For (un)subscribe requests visit
>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>> send a mail to gmx-users-request at gromacs.org.
>> 
> 
> 
> 
> -- 
> Diana Lousa
> Post-doc
> Protein Modeling Laboratory
> ITQB/UNL
> Oeiras, Portugal
> -- 
> Gromacs Users mailing list
> 
> * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting!
> 
> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
> 
> * For (un)subscribe requests visit
> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-request at gromacs.org.



More information about the gromacs.org_gmx-users mailing list