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Navneet Kumar
May 10, 2022, 4:34:13 PM5/10/22
to gmx_MMPBSA
Hi!
I am calculating the binding free energy between two proteins from a simulation trajectory. The final binding energy is coming in positive.
I am using CHARMM36 ff for the simulation.
Please suggest what parameters should I change to get correct estimation of binding free energy.
I have used the following parameter file.
_____________________________________________________________________________________________________________________________________________________
Sample input file for PB calculation
This input file is meant to show only that gmx_MMPBSA works. Although, we tried to use the input files as recommended
in the Amber manual, some parameters have been changed to perform more expensive calculations in a reasonable amount of time. Feel free to change the
parameters according to what is better for your system.
&general
sys_name="Prot-Lig-CHARMM",
startframe=24990,
endframe=25000,
# In gmx_MMPBSA v1.5.0 we have added a new PB radii set named charmm_radii. This radii set should be used only
# with systems prepared with CHARMM force fields. Uncomment the line below to use charmm_radii set
#PBRadii=7,
/
&pb
# radiopt=0 is recommended which means using radii from the prmtop file for both the PB calculation and for the NP
# calculation
istrng=0.15, fillratio=4.0, radiopt=0
/
This input file is meant to show only that gmx_MMPBSA works. Although, we tried to use the input files as recommended
in the Amber manual, some parameters have been changed to perform more expensive calculations in a reasonable amount of time. Feel free to change the
parameters according to what is better for your system.
&general
sys_name="Prot-Lig-CHARMM",
startframe=24990,
endframe=25000,
# In gmx_MMPBSA v1.5.0 we have added a new PB radii set named charmm_radii. This radii set should be used only
# with systems prepared with CHARMM force fields. Uncomment the line below to use charmm_radii set
#PBRadii=7,
/
&pb
# radiopt=0 is recommended which means using radii from the prmtop file for both the PB calculation and for the NP
# calculation
istrng=0.15, fillratio=4.0, radiopt=0
/
______________________________________________________________________________________________________________________________________________
Output and Log files are
____________________________________________________________________________________________________________________________________
| Run on Wed May 11 01:42:15 2022
|
|gmx_MMPBSA Version=v1.5.2+19.g59bff94 based on MMPBSA.py v.16.0
|Complex Structure file: ../md_0_10.tpr
|Complex (GROMACS) topology file: ../topol.top
|Complex (AMBER) topology file: COM.prmtop
|Receptor (AMBER) topology file: REC.prmtop
|Ligand (AMBER) topology file: LIG.prmtop
|Initial trajectories: COM_traj_0.xtc
|
|Receptor mask: ":1-396,668"
|Ligand mask: ":397-667"
|
|Calculations performed using 11 complex frames
|Poisson Boltzmann calculations performed using internal PBSA solver in sander
|
|Using temperature = 298.15 K)
|All units are reported in kcal/mol
|
|SD - Sample standard deviation, SEM - Sample standard error of the mean
|SD(Prop.), SEM(Prop.) - SD and SEM obtained with propagation of uncertainty formula
|https://en.wikipedia.org/wiki/Propagation_of_uncertainty#Example_formulae
|
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
POISSON BOLTZMANN:
Complex:
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
BOND 2168.13 50.88 50.88 15.34 15.34
ANGLE 5141.78 33.43 33.43 10.08 10.08
DIHED 6091.85 26.44 26.44 7.97 7.97
UB 654.56 11.32 11.32 3.41 3.41
IMP 359.96 12.46 12.46 3.76 3.76
CMAP -356.18 19.91 19.91 6.00 6.00
VDWAALS -4299.48 29.25 29.25 8.82 8.82
EEL -38349.35 86.19 86.19 25.99 25.99
1-4 VDW 1586.90 7.84 7.84 2.36 2.36
1-4 EEL 22653.89 52.10 52.10 15.71 15.71
EPB -11388.39 65.55 65.55 19.77 19.77
ENPOLAR 5178.75 5.77 5.77 1.74 1.74
EDISPER -2960.67 5.25 5.25 1.58 1.58
GGAS -4347.94 127.06 82.66 38.31 24.92
GSOLV -9170.31 66.02 67.01 19.90 20.20
TOTAL -13518.25 143.19 67.35 43.17 20.31
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Receptor:
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
BOND 1308.20 33.89 33.89 10.22 10.22
ANGLE 3084.57 35.45 35.45 10.69 10.69
DIHED 3759.55 20.55 20.55 6.20 6.20
UB 399.42 8.64 8.64 2.61 2.61
IMP 212.56 12.62 12.62 3.81 3.81
CMAP -210.32 15.44 15.44 4.65 4.65
VDWAALS -2579.69 23.59 23.59 7.11 7.11
EEL -22011.52 61.36 61.36 18.50 18.50
1-4 VDW 964.23 12.06 12.06 3.63 3.63
1-4 EEL 13244.99 35.61 35.61 10.74 10.74
EPB -7132.40 36.87 36.87 11.12 11.12
ENPOLAR 3135.98 3.86 3.86 1.16 1.16
EDISPER -1813.84 5.01 5.01 1.51 1.51
GGAS -1828.00 95.05 66.19 28.66 19.96
GSOLV -5810.27 37.41 36.51 11.28 11.01
TOTAL -7638.27 102.15 51.00 30.80 15.38
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Ligand:
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
BOND 859.92 27.53 27.53 8.30 8.30
ANGLE 2057.20 23.37 23.37 7.05 7.05
DIHED 2332.29 19.85 19.85 5.99 5.99
UB 255.14 6.90 6.90 2.08 2.08
IMP 147.40 6.21 6.21 1.87 1.87
CMAP -145.86 6.66 6.66 2.01 2.01
VDWAALS -1596.93 12.46 12.46 3.76 3.76
EEL -16184.73 64.50 64.50 19.45 19.45
1-4 VDW 622.67 11.25 11.25 3.39 3.39
1-4 EEL 9408.90 50.35 50.35 15.18 15.18
EPB -4471.12 63.87 63.87 19.26 19.26
ENPOLAR 2141.82 4.87 4.87 1.47 1.47
EDISPER -1344.65 5.15 5.15 1.55 1.55
GGAS -2243.98 93.84 65.41 28.29 19.72
GSOLV -3673.96 64.26 64.27 19.38 19.38
TOTAL -5917.94 113.74 33.50 34.29 10.10
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Delta (Complex - Receptor - Ligand):
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
ΔBOND -0.00 10.53 0.00 3.18 0.00
ΔANGLE 0.00 21.35 0.00 6.44 0.00
ΔDIHED -0.00 13.96 0.00 4.21 0.00
ΔUB -0.00 4.22 0.00 1.27 0.00
ΔIMP 0.00 6.04 0.00 1.82 0.00
ΔCMAP -0.00 2.20 0.00 0.66 0.00
ΔVDWAALS -122.87 6.79 6.03 2.05 1.82
ΔEEL -153.09 39.68 23.72 11.96 7.15
Δ1-4 VDW 0.00 7.03 0.00 2.12 0.00
Δ1-4 EEL 0.00 33.86 0.00 10.21 0.00
ΔEPB 215.14 35.19 24.54 10.61 7.40
ΔENPOLAR -99.05 2.96 2.89 0.89 0.87
ΔEDISPER 197.83 4.91 2.80 1.48 0.84
ΔGGAS -275.96 40.99 25.51 12.36 7.69
ΔGSOLV 313.92 35.65 24.03 10.75 7.25
ΔTOTAL 37.96 54.32 7.86 16.38 2.37
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
|
|gmx_MMPBSA Version=v1.5.2+19.g59bff94 based on MMPBSA.py v.16.0
|Complex Structure file: ../md_0_10.tpr
|Complex (GROMACS) topology file: ../topol.top
|Complex (AMBER) topology file: COM.prmtop
|Receptor (AMBER) topology file: REC.prmtop
|Ligand (AMBER) topology file: LIG.prmtop
|Initial trajectories: COM_traj_0.xtc
|
|Receptor mask: ":1-396,668"
|Ligand mask: ":397-667"
|
|Calculations performed using 11 complex frames
|Poisson Boltzmann calculations performed using internal PBSA solver in sander
|
|Using temperature = 298.15 K)
|All units are reported in kcal/mol
|
|SD - Sample standard deviation, SEM - Sample standard error of the mean
|SD(Prop.), SEM(Prop.) - SD and SEM obtained with propagation of uncertainty formula
|https://en.wikipedia.org/wiki/Propagation_of_uncertainty#Example_formulae
|
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
POISSON BOLTZMANN:
Complex:
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
BOND 2168.13 50.88 50.88 15.34 15.34
ANGLE 5141.78 33.43 33.43 10.08 10.08
DIHED 6091.85 26.44 26.44 7.97 7.97
UB 654.56 11.32 11.32 3.41 3.41
IMP 359.96 12.46 12.46 3.76 3.76
CMAP -356.18 19.91 19.91 6.00 6.00
VDWAALS -4299.48 29.25 29.25 8.82 8.82
EEL -38349.35 86.19 86.19 25.99 25.99
1-4 VDW 1586.90 7.84 7.84 2.36 2.36
1-4 EEL 22653.89 52.10 52.10 15.71 15.71
EPB -11388.39 65.55 65.55 19.77 19.77
ENPOLAR 5178.75 5.77 5.77 1.74 1.74
EDISPER -2960.67 5.25 5.25 1.58 1.58
GGAS -4347.94 127.06 82.66 38.31 24.92
GSOLV -9170.31 66.02 67.01 19.90 20.20
TOTAL -13518.25 143.19 67.35 43.17 20.31
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Receptor:
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
BOND 1308.20 33.89 33.89 10.22 10.22
ANGLE 3084.57 35.45 35.45 10.69 10.69
DIHED 3759.55 20.55 20.55 6.20 6.20
UB 399.42 8.64 8.64 2.61 2.61
IMP 212.56 12.62 12.62 3.81 3.81
CMAP -210.32 15.44 15.44 4.65 4.65
VDWAALS -2579.69 23.59 23.59 7.11 7.11
EEL -22011.52 61.36 61.36 18.50 18.50
1-4 VDW 964.23 12.06 12.06 3.63 3.63
1-4 EEL 13244.99 35.61 35.61 10.74 10.74
EPB -7132.40 36.87 36.87 11.12 11.12
ENPOLAR 3135.98 3.86 3.86 1.16 1.16
EDISPER -1813.84 5.01 5.01 1.51 1.51
GGAS -1828.00 95.05 66.19 28.66 19.96
GSOLV -5810.27 37.41 36.51 11.28 11.01
TOTAL -7638.27 102.15 51.00 30.80 15.38
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Ligand:
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
BOND 859.92 27.53 27.53 8.30 8.30
ANGLE 2057.20 23.37 23.37 7.05 7.05
DIHED 2332.29 19.85 19.85 5.99 5.99
UB 255.14 6.90 6.90 2.08 2.08
IMP 147.40 6.21 6.21 1.87 1.87
CMAP -145.86 6.66 6.66 2.01 2.01
VDWAALS -1596.93 12.46 12.46 3.76 3.76
EEL -16184.73 64.50 64.50 19.45 19.45
1-4 VDW 622.67 11.25 11.25 3.39 3.39
1-4 EEL 9408.90 50.35 50.35 15.18 15.18
EPB -4471.12 63.87 63.87 19.26 19.26
ENPOLAR 2141.82 4.87 4.87 1.47 1.47
EDISPER -1344.65 5.15 5.15 1.55 1.55
GGAS -2243.98 93.84 65.41 28.29 19.72
GSOLV -3673.96 64.26 64.27 19.38 19.38
TOTAL -5917.94 113.74 33.50 34.29 10.10
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Delta (Complex - Receptor - Ligand):
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
ΔBOND -0.00 10.53 0.00 3.18 0.00
ΔANGLE 0.00 21.35 0.00 6.44 0.00
ΔDIHED -0.00 13.96 0.00 4.21 0.00
ΔUB -0.00 4.22 0.00 1.27 0.00
ΔIMP 0.00 6.04 0.00 1.82 0.00
ΔCMAP -0.00 2.20 0.00 0.66 0.00
ΔVDWAALS -122.87 6.79 6.03 2.05 1.82
ΔEEL -153.09 39.68 23.72 11.96 7.15
Δ1-4 VDW 0.00 7.03 0.00 2.12 0.00
Δ1-4 EEL 0.00 33.86 0.00 10.21 0.00
ΔEPB 215.14 35.19 24.54 10.61 7.40
ΔENPOLAR -99.05 2.96 2.89 0.89 0.87
ΔEDISPER 197.83 4.91 2.80 1.48 0.84
ΔGGAS -275.96 40.99 25.51 12.36 7.69
ΔGSOLV 313.92 35.65 24.03 10.75 7.25
ΔTOTAL 37.96 54.32 7.86 16.38 2.37
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
--
Thanks & Regards
_______________________________________________________
| |||||||||||||||||||||||
marioe911116
May 10, 2022, 8:29:25 PM5/10/22
to gmx_MMPBSA
I see you are using only 11 frames... please try with more frames (100 minimum) and also check this section in the docs (https://valdes-tresanco-ms.github.io/gmx_MMPBSA/Q%26A/calculations/#possible-solutions_2)... if you want to dismissed the EDISPER term, If you are using a current version (v1.5.2 or the development version), you can generate the output file without having to recalculate the whole system. To do this, in the _GMXMMPBSA_info file set INPUT['inp'] = 1
hth!
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