[gmx-users] Relative binding free energy
Stefania Evoli
stefania.evoli at kaust.edu.sa
Mon Mar 14 15:09:40 CET 2016
Thank you for your time and precious help.
The complete topology is
#include "amber99sb.ff/forcefield.itp"
; Gly_GMX.top created by acpype (Rev: 403) on Wed Jan 20 13:39:56 2016
;[ defaults ]
; nbfunc comb-rule gen-pairs fudgeLJ fudgeQQ
;1 2 yes 0.5 0.8333
[ atomtypes ]
; name bond_type mass charge ptype
sigma epsilon
n4 n4 0.00000 0.00000 A
3.25000e-01 7.11280e-01
c3 c3 0.00000 0.00000 A
3.39967e-01 4.57730e-01
c c 0.00000 0.00000 A
3.39967e-01 3.59824e-01
o o 0.00000 0.00000 A
2.95992e-01 8.78640e-01
hx hx 0.00000 0.00000 A
1.95998e-01 6.56888e-02
hn hn 0.00000 0.00000 A
1.06908e-01 6.56888e-02
n4 n4 0.00000 0.00000 A
3.25000e-01 7.11280e-01
c3 c3 0.00000 0.00000 A
3.39967e-01 4.57730e-01
c c 0.00000 0.00000 A
3.39967e-01 3.59824e-01
o o 0.00000 0.00000 A
2.95992e-01 8.78640e-01
oh oh 0.00000 0.00000 A
3.06647e-01 8.80314e-01
hx hx 0.00000 0.00000 A
1.95998e-01 6.56888e-02
h1 h1 0.00000 0.00000 A
2.47135e-01 6.56888e-02
ho ho 0.00000 0.00000 A
0.00000e+00 0.00000e+00
hn hn 0.00000 0.00000 A
1.06908e-01 6.56888e-02
c3_dummy c3 0.00000 0.00000 A
3.39967e-01 0.00000e+00
hx_dummy hx 0.00000 0.00000 A
1.95998e-01 0.00000e+00
oh_dummy oh 0.00000 0.00000 A
3.06647e-01 0.00000e+00
h1_dummy h1 0.00000 0.00000 A
2.47135e-01 0.00000e+00
ho_dummy ho 0.00000 0.00000 A
0.00000e+00 0.00000e+00
[ moleculetype ]
;name nrexcl
LIG 3
[ atoms ]
; nr type resnr res atom cgnr charge mass
typeB chargeB massB comments
1 c 1 LIG C1 1 0.932601 12.01000
c 0.935601 12.01000 ; MCSS
2 c3 1 LIG CA1 2 -0.095200 12.01000
c3 -0.126500 12.01000 ; MCSS
3 c3_dummy 1 LIG CB1 3 0.00000 12.01000
c3 0.136400 12.01000 ; to be appeared
4 hx 1 LIG HA1 4 0.088700 1.00800
hx_dummy 0.00000 1.00800 ; to be annihilated
5 hx 1 LIG HA2 5 0.088700 1.00800
hx 0.094700 1.00800 ; MCSS
6 h1_dummy 1 LIG HB1 6 0.00000 1.00800
h1 0.068200 1.00800 ; to be appeared
7 h1_dummy 1 LIG HB2 7 0.00000 1.00800
h1 0.068200 1.00800 ; to be appeared
8 ho_dummy 1 LIG HG1 8 0.00000 1.00800
ho 0.448000 1.00800 ; to be appeared
9 n4 1 LIG N1 9 -0.835601 14.01000
n4 -0.822601 14.01000 ; MCSS
10 o 1 LIG O1 10 -0.755301 16.00000
o -0.759801 16.00000 ; MCSS
11 oh_dummy 1 LIG OG1 11 0.00000 16.00000
oh -0.628801 16.00000 ; to be appeared
12 o 1 LIG OXT1 12 -0.755301 16.00000
o -0.759801 16.00000 ; MCSS
13 hn 1 LIG H1 13 0.443800 1.00800
hn 0.448800 1.00800 ; MCSS
14 hn 1 LIG H2 14 0.443800 1.00800
hn 0.448800 1.00800 ; MCSS
15 hn 1 LIG H3 15 0.443800 1.00800
hn 0.448800 1.00800 ; MCSS
[ bonds ]
; atomnrs funct <<<<<<<<<<<<<<<<parametersA
<<<<<<<<<<<<<<<<<<<<<<<<parametersB
9 13 1 1.0330e-01 3.0878e+05 1.0330e-01
3.0878e+05
9 14 1 1.0330e-01 3.0878e+05 1.0330e-01
3.0878e+05
9 15 1 1.0330e-01 3.0878e+05 1.0330e-01
3.0878e+05
9 2 1 1.4990e-01 2.4568e+05 1.4990e-01
2.4568e+05
2 4 1 1.0910e-01 2.8342e+05 1.0910e-01
2.8342e+05
2 5 1 1.0910e-01 2.8342e+05 1.0910e-01
2.8342e+05
2 1 1 1.5080e-01 2.7472e+05 1.5080e-01
2.7472e+05
1 10 1 1.2140e-01 5.4225e+05 1.2140e-01
5.4225e+05
1 12 1 1.2140e-01 5.4225e+05 1.2140e-01
5.4225e+05
2 3 1 1.5350e-01 2.5363e+05 1.5350e-01
2.5363e+05
3 6 1 1.0930e-01 2.8108e+05 1.0930e-01
2.8108e+05
3 7 1 1.0930e-01 2.8108e+05 1.0930e-01
2.8108e+05
3 11 1 1.4260e-01 2.6284e+05 1.4260e-01
2.6284e+05
11 8 1 9.7400e-02 3.0928e+05 9.7400e-02
3.0928e+05
[ pairs ]
; ai aj funct
1 6 1
1 7 1
1 11 1
1 13 1
1 14 1
1 15 1
2 8 1
3 10 1
3 12 1
3 13 1
3 14 1
3 15 1
4 10 1
4 12 1
4 13 1
4 14 1
4 15 1
5 6 1
5 7 1
5 10 1
5 11 1
5 12 1
5 13 1
5 14 1
5 15 1
6 8 1
6 9 1
7 8 1
7 9 1
9 10 1
9 11 1
9 12 1
[ angles ]
; atomnrs funct <<<<<<<<<<<<<<<<parametersA
<<<<<<<<<<<<<<<<<<<<<<<<parametersB
9 2 4 1 1.0791e+02 4.1020e+02
1.0791e+02 4.1020e+02
9 2 5 1 1.0791e+02 4.1020e+02
1.0791e+02 4.1020e+02
9 2 1 1 1.1421e+02 5.4451e+02
1.1421e+02 5.4451e+02
13 9 14 1 1.0811e+02 3.3907e+02
1.0811e+02 3.3907e+02
13 9 15 1 1.0811e+02 3.3907e+02
1.0811e+02 3.3907e+02
14 9 15 1 1.0811e+02 3.3907e+02
1.0811e+02 3.3907e+02
2 9 13 1 1.1011e+02 3.8652e+02
1.1011e+02 3.8652e+02
2 9 14 1 1.1011e+02 3.8652e+02
1.1011e+02 3.8652e+02
2 9 15 1 1.1011e+02 3.8652e+02
1.1011e+02 3.8652e+02
2 1 10 1 1.2311e+02 5.6928e+02
1.2311e+02 5.6928e+02
2 1 12 1 1.2311e+02 5.6928e+02
1.2311e+02 5.6928e+02
4 2 5 1 1.1074e+02 3.2669e+02
1.1074e+02 3.2669e+02
1 2 4 1 1.0954e+02 3.9522e+02
1.0954e+02 3.9522e+02
1 2 5 1 1.0954e+02 3.9522e+02
1.0954e+02 3.9522e+02
10 1 12 1 1.3038e+02 6.5413e+02
1.3038e+02 6.5413e+02
9 2 3 1 1.1432e+02 5.3932e+02
1.1432e+02 5.3932e+02
2 3 6 1 1.1007e+02 3.8794e+02
1.1007e+02 3.8794e+02
2 3 7 1 1.1007e+02 3.8794e+02
1.1007e+02 3.8794e+02
2 3 11 1 1.0943e+02 5.6668e+02
1.0943e+02 5.6668e+02
1 2 3 1 1.1053e+02 5.3379e+02
1.1053e+02 5.3379e+02
3 2 5 1 1.1174e+02 3.8510e+02
1.1174e+02 3.8510e+02
3 11 8 1 1.0816e+02 3.9405e+02
1.0816e+02 3.9405e+02
6 3 7 1 1.0955e+02 3.2786e+02
1.0955e+02 3.2786e+02
11 3 6 1 1.0988e+02 4.2652e+02
1.0988e+02 4.2652e+02
11 3 7 1 1.0988e+02 4.2652e+02
1.0988e+02 4.2652e+02
[ dihedrals ]
; atomnrs funct <<<<<<<<<<<<<<<<parametersA
<<<<<<<<<<<<<<<<<<<<<<<<parametersB
9 2 1 10 9 180.00 0.00000 2
180.00 0.00000 2
9 2 1 12 9 180.00 0.00000 2
180.00 0.00000 2
13 9 2 4 9 0.00 0.65084 3
0.00 0.65084 3
13 9 2 5 9 0.00 0.65084 3
0.00 0.65084 3
13 9 2 1 9 0.00 0.65084 3
0.00 0.65084 3
14 9 2 4 9 0.00 0.65084 3
0.00 0.65084 3
14 9 2 5 9 0.00 0.65084 3
0.00 0.65084 3
14 9 2 1 9 0.00 0.65084 3
0.00 0.65084 3
15 9 2 4 9 0.00 0.65084 3
0.00 0.65084 3
15 9 2 5 9 0.00 0.65084 3
0.00 0.65084 3
15 9 2 1 9 0.00 0.65084 3
0.00 0.65084 3
10 1 2 4 9 180.00 0.00000 2
180.00 0.00000 2
10 1 2 5 9 180.00 0.00000 2
180.00 0.00000 2
12 1 2 4 9 180.00 0.00000 2
180.00 0.00000 2
12 1 2 5 9 180.00 0.00000 2
180.00 0.00000 2
9 2 3 6 9 0.00 0.65084 3
0.00 0.65084 3
9 2 3 7 9 0.00 0.65084 3
0.00 0.65084 3
9 2 3 11 9 0.00 0.65084 3
0.00 0.65084 3
14 9 2 3 9 0.00 0.65084 3
0.00 0.65084 3
15 9 2 3 9 0.00 0.65084 3
0.00 0.65084 3
13 9 2 3 9 0.00 0.65084 3
0.00 0.65084 3
2 3 11 8 9 0.00 0.66944 3
0.00 0.00000 3
2 3 11 8 9 0.00 0.00000 1
0.00 1.04600 1
2 3 11 8 9 0.00 1.04600 1
0.00 1.04600 1
5 2 3 6 9 0.00 0.65084 3
0.00 0.65084 3
5 2 3 7 9 0.00 0.65084 3
0.00 0.65084 3
1 2 3 6 9 0.00 0.65084 3
0.00 0.65084 3
1 2 3 7 9 0.00 0.65084 3
0.00 0.65084 3
1 2 3 11 9 0.00 0.65084 3
0.00 0.65084 3
10 1 2 3 9 180.00 0.00000 2
180.00 0.00000 2
12 1 2 3 9 180.00 0.00000 2
180.00 0.00000 2
6 3 11 8 9 0.00 0.69733 3
0.00 0.69733 3
7 3 11 8 9 0.00 0.69733 3
0.00 0.69733 3
11 3 2 5 9 0.00 0.65084 3
0.00 0.65084 3
[ dihedrals ]
; atomnrs funct <<<<<<<<<<<<<<<<parametersA
<<<<<<<<<<<<<<<<<<<<<<<<parametersB
2 10 1 12 4 180.00 4.60240 2
180.00 4.60240 2
; Include water topology
#include "amber99sb-ildn.ff/tip3p.itp"
[ system ]
LIG
[ molecules ]
; Compound nmols
LIG 1
SOL 3719
Please, could you give a look at that? I obtained it by using the useful
tool described in the article 'A Python tool to set up relative free
energy calculations in GROMACS¹ Pavel V. Klimovich and David L. Mobley.
Probably I¹m doing something wrong in the MCSS map.
You mentioned that I can simultaneously switch off the charges for
disappearing groups and switch on for the appearing groups with a single
lambda path. Could you clarify this point and if it is possible suggest me
someway to do that, please?
Thank you!
‹Dr. Stefania Evoli
Post-Doctoral Fellow
King Abdullah University of Science and Technology
Catalysis center - Bldg. 3, 4th floor, 4231WS18
Thuwal, Kingdom of Saudi Arabia
stefania.evoli at kaust.edu.sa
On 3/14/16, 4:33 PM, "gromacs.org_gmx-users-bounces at maillist.sys.kth.se on
behalf of Hannes Loeffler"
<gromacs.org_gmx-users-bounces at maillist.sys.kth.se on behalf of
Hannes.Loeffler at stfc.ac.uk> wrote:
>I had a quick look at this and I see quite a few problems there.
>
>You don't show the [atomtypes] but I suppose that whatever you call
>*_dummy has zero vdW parameters. BTW, there is no need to invent
>different atom type names for every dummy as their non-bonded parameters
>are all zero anyway and bonded terms are indexed.
>
>You say this is single topology, well it is, but only almost. You make
>the alpha-H in glycine and the beta-C in serine a dummy which means
>that you are duplicating. A possible problem with this is that any
>intermediate state has the alpha-C now five-fold coordinated! You
>should always be wary of such setups because this will introduce
>additional bonded terms (you don't show them) that are not present in
>the end state and can therefore distort the molecule and also lead to
>instabilities.
>
>Another problem with this is that you have dummy atoms at both end
>states. With Gromacs you will need _two_ topolgies to ensure that you
>change electrostatics and vdW in the correct order. You will need to
>first switch off the charges on the disappearing group followed by
>modifying the vdW parameters between the end states (you can do that
>simultaneously that is switch off for disappearing groups and switch on
>for the appearing groups with a single lambda path). Eventually, you
>switch on the charges for the appearing group. There are some
>varieties in how to do this in practice but that's basically it.
>
>So you have used a MCSS to do the mapping and I guess the algorithm
>that you have used actually mapped the alpha-H with beta-C. I suggest
>that you keep it that way to truly have a single topology description
>as explained above. BTW, the typical MCSS algorithm is 2D only and as
>such has no idea about stereochemistry. So make sure that the right
>hydrogen maps to the right carbon atom (you say you have D-serine).
>
>Judging from the atom type names it looks to me that those are GAFF
>types. If so I suggest to actually use AMBER peptide parameters (may
>be available in the literature or online for single residue zwitterions)
>esp. when used together with a protein. A particular problem here is
>that charge derivation will happen in the gas phase and you have
>zwitterions! Geometry optimisation of such structures will very likely
>lead to rather distorted and unnatural conformations.
>
>HTH,
>Hannes.
>
>
>On Mon, 14 Mar 2016 12:00:28 +0000
>Stefania Evoli <stefania.evoli at kaust.edu.sa> wrote:
>
>> The [atom] section of the single topology of my transformation looks
>> like
>>
>> [ atoms ]
>> ; nr type resnr res atom cgnr charge mass
>> typeB chargeB massB comments
>> 1 c 1 LIG C1 1 0.932601 12.01000
>> c 0.935601 12.01000 ; MCSS
>> 2 c3 1 LIG CA1 2 -0.095200 12.01000
>> c3 -0.126500 12.01000 ; MCSS
>> 3 c3_dummy 1 LIG CB1 3 0.00000 12.01000
>> c3 0.136400 12.01000 ; to be appeared
>> 4 hx 1 LIG HA1 4 0.088700 1.00800
>> hx_dummy 0.00000 1.00800 ; to be annihilated
>> 5 hx 1 LIG HA2 5 0.088700 1.00800
>> hx 0.094700 1.00800 ; MCSS
>> 6 h1_dummy 1 LIG HB1 6 0.00000 1.00800
>> h1 0.068200 1.00800 ; to be appeared
>> 7 h1_dummy 1 LIG HB2 7 0.00000 1.00800
>> h1 0.068200 1.00800 ; to be appeared
>> 8 ho_dummy 1 LIG HG1 8 0.00000 1.00800
>> ho 0.448000 1.00800 ; to be appeared
>> 9 n4 1 LIG N1 9 -0.835601 14.01000
>> n4 -0.822601 14.01000 ; MCSS
>> 10 o 1 LIG O1 10 -0.755301 16.00000
>> o -0.759801 16.00000 ; MCSS
>> 11 oh_dummy 1 LIG OG1 11 0.00000 16.00000
>> oh -0.628801 16.00000 ; to be appeared
>> 12 o 1 LIG OXT1 12 -0.755301 16.00000
>> o -0.759801 16.00000 ; MCSS
>> 13 hn 1 LIG H1 13 0.443800 1.00800
>> hn 0.448800 1.00800 ; MCSS
>> 14 hn 1 LIG H2 14 0.443800 1.00800
>> hn 0.448800 1.00800 ; MCSS
>> 15 hn 1 LIG H3 15 0.443800 1.00800
>> hn 0.448800 1.00800 ; MCSS
>--
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