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CHARMM力场MMPBSA计算在本例中，需要的文件有MD结构+质量（db）文件，即.tpr文件；一个ndx文件（标注配体和受体的编号）；一个.xtc文件；一个top文件；还有一个后缀名为in的输入文件。构建.ndx这一步使用gmx生成配体和受体的ndx，需要复合物的.gro文件，通过选择原子编号来确定两个部分。 gmx make_ndx -f your_grofile.gro -o index.ndx
splitch 1 #此时会生成新的组和编号
name ligand_index ligand #ligand_index代表index的编号，下同
name receptor_index receptor
q #save and quit构建.inhttp://mmpbsa.in作为输入文件，规定了多个参数。 Sample input file for PB calculation
This input file is meant to show only that gmx_MMPBSA works. Althought,
we tried to used 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=1, #始末帧数
endframe=800,
# 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=5,
/
&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
/计算MMPBSA激活gmxMMPBSA环境 conda activate gmxMMPBSA在conda的gmxMMPBSA环境下计算MMPBSA，这一步计算需要耗费较长时间。 mpirun -np 2 gmx_MMPBSA MPI -O -i mmpbsa.in -cs md_50.tpr -ci index_0615.ndx -cg 20 19 -ct mono28_0614.xtc -cp mono28_0615.top -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv结果分析具体的解析参考官网outfiles部分的说明。 在FINAL_RESULTS_MMPBSA.dat中，会分别给出配体、受体、复合物各能量项的数值。 | Run on Sun Jun 26 14:49:39 2022
|
|gmx_MMPBSA Version=v1.5.5 based on MMPBSA.py v.16.0
|Complex Structure file: md_50.tpr
|Complex (GROMACS) topology file: mono28_0615.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: ":29-334"
|Ligand mask: ":1-28"
|
|Calculations performed using 800 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 1078.82 28.42 28.42 1.00 1.00
ANGLE 2420.92 37.12 37.12 1.31 1.31
DIHED 3189.31 21.52 21.52 0.76 0.76
UB 285.63 7.13 7.13 0.25 0.25
IMP 173.05 8.90 8.90 0.31 0.31
CMAP -277.36 13.28 13.28 0.47 0.47
VDWAALS -2212.99 21.96 21.96 0.78 0.78
EEL -3124.35 412.28 412.28 14.58 14.58
1-4 VDW 907.35 14.72 14.72 0.52 0.52
1-4 EEL 15590.87 53.59 53.59 1.89 1.89
EPB -22170.24 404.71 404.71 14.31 14.31
ENPOLAR 2631.66 8.98 8.98 0.32 0.32
EDISPER -1495.02 10.81 10.81 0.38 0.38
GGAS 18031.25 420.13 415.11 14.85 14.68
GSOLV -21033.60 404.95 402.93 14.32 14.25
TOTAL -3002.35 583.52 56.24 20.63 1.99
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Receptor:
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
BOND 993.46 26.89 26.89 0.95 0.95
ANGLE 2301.53 35.85 35.85 1.27 1.27
DIHED 2999.36 20.22 20.22 0.71 0.71
UB 277.80 6.96 6.96 0.25 0.25
IMP 160.93 8.51 8.51 0.30 0.30
CMAP -149.34 12.36 12.36 0.44 0.44
VDWAALS -2118.18 21.27 21.27 0.75 0.75
EEL -18691.52 78.49 78.49 2.77 2.77
1-4 VDW 884.69 14.55 14.55 0.51 0.51
1-4 EEL 13247.11 51.03 51.03 1.80 1.80
EPB -3061.55 57.54 57.54 2.03 2.03
ENPOLAR 2338.10 8.00 8.00 0.28 0.28
EDISPER -1301.54 9.36 9.36 0.33 0.33
GGAS -94.15 110.09 77.56 3.89 2.74
GSOLV -2025.00 58.84 58.21 2.08 2.06
TOTAL -2119.14 124.82 51.64 4.41 1.83
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Ligand:
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
BOND 85.37 7.48 7.48 0.26 0.26
ANGLE 119.39 8.98 8.98 0.32 0.32
DIHED 189.95 6.43 6.43 0.23 0.23
UB 7.82 1.38 1.38 0.05 0.05
IMP 12.12 2.66 2.66 0.09 0.09
CMAP -128.02 4.82 4.82 0.17 0.17
VDWAALS -70.23 2.71 2.71 0.10 0.10
EEL 14900.60 361.64 361.64 12.79 12.79
1-4 VDW 22.66 2.68 2.68 0.09 0.09
1-4 EEL 2343.75 12.31 12.31 0.44 0.44
EPB -18492.07 354.60 354.60 12.54 12.54
ENPOLAR 324.04 2.14 2.14 0.08 0.08
EDISPER -245.54 3.41 3.41 0.12 0.12
GGAS 17483.41 362.16 358.84 12.80 12.69
GSOLV -18413.57 354.62 353.13 12.54 12.49
TOTAL -930.16 506.87 18.66 17.92 0.66
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Delta (Complex - Receptor - Ligand):
Energy Component Average SD(Prop.) SD SEM(Prop.) SEM
-------------------------------------------------------------------------------
ΔBOND 0.00 5.95 0.00 0.21 0.00
ΔANGLE 0.00 7.71 0.00 0.27 0.00
ΔDIHED -0.00 5.13 0.00 0.18 0.00
ΔUB 0.00 1.21 0.00 0.04 0.00
ΔIMP -0.00 2.26 0.00 0.08 0.00
ΔCMAP 0.00 3.91 0.00 0.14 0.00
ΔVDWAALS -24.58 2.02 4.82 0.07 0.17
ΔEEL 666.57 27.84 162.19 0.98 5.73
Δ1-4 VDW -0.00 2.50 0.00 0.09 0.00
Δ1-4 EEL 0.00 9.74 0.00 0.34 0.00
ΔEPB -616.61 7.42 160.77 0.26 5.68
ΔENPOLAR -30.49 1.16 5.05 0.04 0.18
ΔEDISPER 52.06 1.96 6.76 0.07 0.24
ΔGGAS 641.99 28.31 163.50 1.00 5.78
ΔGSOLV -595.04 7.76 161.87 0.27 5.72
ΔTOTAL 46.95 29.35 9.63 1.04 0.34
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------要看ddG，只需关注最后的Delta部分。这里的ΔTOTAL是正的，原因在ΔEDISPER这一项，通过修改http://mmpbsa.in文件，可以选择不计算该项： Sample input file for PB calculation
This input file is meant to show only that gmx_MMPBSA works. Althought,
we tried to used 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=1, #始末帧数
endframe=800,
# 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=5,
/
&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, inp=1, use_sav=0
/添加 inp=1, use_sav=0 之后，SASA项的能量为γSASA，再重新计算一次，ddG会显著降低。具体参看Positive Binding Energy 原文链接： https://zhuanlan.zhihu.com/p/528893992 |