[gmx-users] question of perturbing order in single topology FEP, gromacs

Peng He hepeng.yanglu at gmail.com
Wed Nov 29 20:56:41 CET 2017


Hi, Asaf,

Thank you very much for your suggestions, I am not sure I understand it
correctly.

2017-11-29 13:22 GMT-05:00 <asaffarhi at post.tau.ac.il>:

> Dear Peng,
>
> You can transform each of the molecules seperately.

You can remove the nonbonded interactions of the atoms that are different
> between the compared molecules.
>
Does it mean when going from A-B to A-C, decouple the B's nonbonded than
coupling the C's nonbonded interaction?

> Then, if you have only one dihedral relating the different atoms to the
> common atoms in each molecule it does not need to be removed. Also, the
> bond angle and covalent bond terms do not need to be removed. This is based
> on NVT but may be also accurate for NPT.
>
In the Ethane -> methanol case, the C-C bond length decreases from 1.5 to
1.4 when perturbing to C-O bond, and the kappa for the bond also changes, I
am not sure but I think we can use bonded lambdas to perturb the bond, I
did not remove any bond or angle in this case.
I think what you suggest is dual topology method which contains a dummy CH3
group in Methanol and a dummy OH group in Ethane, in that case I don't need
to change the bond length and angle, and it would not create such different
free energy values. I really test it in dual topology method and there is
little effect from the order of perturbations.
>
> We also saw that the order of transforming matters but maybe you can try
> without removing the bonded terms.


> For more details you can read:
> http://www.sciencedirect.com/science/article/pii/S0010465516303411
>
> Best,
> Asaf
>
>
> Quoting Peng He <hepeng.yanglu at gmail.com>:
>
> HI, all,
>>
>> I am recently doing some test FEP calculations to get familiar, I am
>> preparing a system of ethane -> methanol using Amber gaff force field and
>> single topology method.
>>
>> "  4 [ atomtypes ]
>>   5 ;name   bond_type     mass     charge   ptype   sigma         epsilon
>>     Amb
>>   6  c3       c3          0.00000  0.00000   A     3.39967e-01
>> 4.57730e-01 ; 1.91  0.1094
>>   7  hc       hc          0.00000  0.00000   A     2.64953e-01
>> 6.56888e-02 ; 1.49  0.0157
>>   8  oh       oh          0.00000  0.00000   A     3.06647e-01
>> 8.80314e-01 ; 1.72  0.2104
>>   9  h1       h1          0.00000  0.00000   A     2.47135e-01
>> 6.56888e-02 ; 1.39  0.0157
>>  10  dh       hc          0.00000  0.00000   A     0.00000  0.00000
>>  11  ho       ho          0.00000  0.00000   A     0.00000e+00
>>  0.00000e+00
>>  12 [ moleculetype ]
>>  13 ;name            nrexcl
>>  14  UNK              3
>>  15
>>  16 [ atoms ]
>>  17 ;   nr  type  resi  res  atom  cgnr     charge      mass       ; qtot
>> bond_type
>>  18      1   c3     1   UNK    C1    1    -0.095100     12.01000   c3
>>  0.116700    12.01000
>>  19      2   c3     1   UNK    C2    2    -0.095100     12.01000   oh
>> -0.598801    12.01000
>>  20      3   hc     1   UNK    H1    3     0.031700      1.00800   h1
>>  0.028700     1.00800
>>  21      4   hc     1   UNK    H2    4     0.031700      1.00800   h1
>>  0.028700     1.00800
>>  22      5   hc     1   UNK    H3    5     0.031700      1.00800   h1
>>  0.028700     1.00800
>>  23      6   hc     1   UNK    H4    6     0.031700      1.00800   ho
>>  0.396000     1.00800
>>  24      7   hc     1   UNK    H5    7     0.031700      1.00800   dh
>>  0.000000     1.00800
>>  25      8   hc     1   UNK    H6    8     0.031700      1.00800   dh
>>  0.000000     1.00800
>>  26
>>  27 [ bonds ]
>>  28 ;   ai     aj funct   r             k
>>  29      1      2   1    1.5375e-01    2.5179e+05  1.4233e-01
>> 2.6501e+05
>>  30      1      3   1    1.0969e-01    2.7665e+05  1.0969e-01
>> 2.7665e+05
>>  31      1      4   1    1.0969e-01    2.7665e+05  1.0969e-01
>> 2.7665e+05
>>  32      1      5   1    1.0969e-01    2.7665e+05  1.0969e-01
>> 2.7665e+05
>>  33      2      6   1    1.0969e-01    2.7665e+05  9.7300e-02
>> 3.1079e+05
>>  34      2      7   1    1.0969e-01    2.7665e+05  1.0969e-01
>> 2.7665e+05
>>  35      2      8   1    1.0969e-01    2.7665e+05  1.0969e-01
>> 2.7665e+05
>> ...
>> ..."
>>
>> I know to perturbing from large molecule(ethane) to small(methanol), I
>> need
>> to perturb the electrostatic interaction first than vdw, But I don't know
>> where to perturb the bonded lambdas. I have tested different orders of
>> Bonded lambdas, and I have got a quite different answer which seems odd to
>> me. I have a table for that
>> stage1 stage2 stage3 dG(kj) dG(kcal)
>> single topology solv q/bonded/vdw -14.36 -3.43
>> bonded q vdw -13.79 -3.30
>> bonded/q vdw -14.91 -3.56
>> q bonded vdw -17.13 -4.09
>> q bonded/vdw -20.22 -4.83
>> q vdw bonded -25.2 -6.02
>> single topology vac q/bonded/vdw 10.32 2.47
>> bonded q vdw 9.53 2.28
>> bonded/q vdw 9.1 2.17
>> q bonded vdw 8.71 2.08
>> q bonded/vdw 9.64 2.30
>> q vdw bonded 9.84 2.35
>> The desolvation free energy of ethane is -2.48 and methanol 3.48kcal.
>> The best result which close the cyclo for ethane,vac -> ethane, solv ->
>> methanol, solv -> methanol,vac -> ethane,vac is perturbing all three
>> together(q/bonded/vdw) followed by perturbing bonded/q together then vdw.
>> The worst is to decouple bonded lambdas the last. When I try dual topology
>> method, there is no such difference where to place the bonded lambdas...
>>
>>  I am confused that which one should used and why others are not OK?
>>
>> Thank you
>> Best
>> Peng
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