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

Wed May 27 23:20:00 CEST 2015

On 5/27/15 5:11 PM, Ebert Maximilian wrote:
> 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?
>

Given that the atom types are unchanged and you altered the charges, it suggests 
that the new charges lead to interactions that are too strong.  The balance 
between LJ and electrostatic terms is key to the balance of the nonbonded 
interactions in the force field, so either you need to modify LJ terms (not fun) 
or refine the charges further.

Hydration free energy would be another good target data point.

-Justin

> 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
>>
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-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==================================================