Dear Amber developers,
Regarding multiple trajectory mmPBSA in *“MMPBSA.py.MPI”*, when we use
single trajectory mmPBSA to calculate ddGbinding, the R^2 is around
0.6~0.7. Since there is a certain degree of induced fit effect of the
enzyme, we try to use multiple trajectory mmPBSA to improve the result.
However, after using the following setting of multiple trajectory mmPBSA,
the R^2 becomes almost 0, meaning something must be wrong.
Here is the question:
1. For the multiple trajectory mmPBSA in “MMPBSA.py.MPI”, do we have
to offer solvated or gas phase ligand and receptor .mdcrd in the “-yr” and
“-yl” setting? Or both are fine?
-yr solvated_receptor.mdcrd
-yl solvated_ligand.mdcrd
-slp solvated_ligand.prmtop
-srp solvated_receptor.prmtop
2. For any MD calculation, the RMSD of the backbone should be
converged. However, when we do solvated_ligand production run, the
solvated ligand just swim around in the solvated box freely, even we set a
restraint on the ligand. Therefore, the RMSD of the solvated ligand just
goes all the way from 0 to 40. We wonder if this non-converged solvated
ligand simulation will deteriorate the mmPBSA result? Or this is fine
since we are trying to sample more ligand conformation?
*Here is the setting for single trajectory mmPBSA that we use.*
=====================================================================
$AMBERHOME/bin/MMPBSA.py -O
-i mmpbsa.in
-o FINAL_RESULTS_MMPBSA.dat
-sp solvated_complex.prmtop
-cp complex.prmtop
-rp receptor.prmtop
-lp ligand.prmtop
-y solvated_complex.mdcrd
*Here is the setting for multiple trajectory mmPBSA.*
$AMBERHOME/bin/MMPBSA.py -O
-i mmpbsa.in
-o FINAL_RESULTS_MMPBSA.dat
-sp solvated_complex.prmtop
-cp complex.prmtop
-rp receptor.prmtop
-lp ligand.prmtop
-y solvated_complex.mdcrd
-yr solvated_receptor.mdcrd
-yl solvated_ligand.mdcrd
-slp solvated_ligand.prmtop
-srp solvated_receptor.prmtop
*Here is one of the results of single trajectory mmPBSA.*
|Input file:
|--------------------------------------------------------------
|Input file for running PB
|&general
| keep_files=2,
|/
|&pb
| istrng=0.100,
|/
|--------------------------------------------------------------
|MMPBSA.py Version=12.0
|Solvated complex topology file: Solvated_complex.prmtop
|Complex topology file: complex.prmtop
|Receptor topology file: receptor.prmtop
|Ligand topology file: ligand.prmtop
|Initial mdcrd(s): Solvated_complex.mdcrd
|
|Receptor mask: ":1-259,261"
|Ligand mask: ":260"
|Ligand residue name is "GRL"
|
|Calculations performed using 2000 complex frames.
|Poisson Boltzmann calculations performed using internal PBSA solver in
mmpbsa_py_energy
|
|All units are reported in kcal/mole.
POISSON BOLTZMANN:
Complex:
Energy Component Average Std. Dev. Std. Err.
of Mean
---------------------------------------------------------------------------------------------
VDWAALS -2087.8382 17.0521 0.3813
EEL -18886.2185 45.2532
1.0119
EPB -2756.8506 32.0416
0.7165
ENPOLAR 1947.5890 4.0342
0.0902
G gas -20974.0567 45.9331
1.0271
G solv -809.2616 31.0811
0.6950
TOTAL -21783.3182 36.1586
0.8085
Receptor:
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
VDWAALS -2043.3834 16.8102 0.3759
EEL -18864.4703 45.1234
1.0090
EPB -2773.0794 32.0809
0.7174
ENPOLAR 1945.4690 3.9431 0.0882
G gas -20907.8537 45.7038
1.0220
G solv -827.6103 31.1457
0.6964
TOTAL -21735.4641 36.0665
0.8065
Ligand:
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
VDWAALS -2.6410 0.5367 0.0120
EEL -3.7266 0.4818
0.0108
EPB -13.4892 0.3867
0.0086
ENPOLAR 29.2052 0.1594 0.0036
G gas -6.3676 0.6201
0.0139
G solv 15.7160 0.4182
0.0094
TOTAL 9.3483 0.5753 0.0129
Differences (Complex - Receptor - Ligand):
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
VDWAALS -41.8137 2.2175 0.0496
EEL -18.0216 2.5808
0.0577
EPB 29.7180 2.0220
0.0452
ENPOLAR -27.0852 0.3851 0.0086
EDISPER 0.0000 0.0000 0.0000
DELTA G gas -59.8353 2.6759 0.0598
DELTA G solv 2.6328 2.1588 0.0483
DELTA TOTAL -57.2025 2.9210 0.0653
-------------------------------------------------------------------------------
*Here is corresponding multiple trajectory mmPBSA*
|Input file:
|--------------------------------------------------------------
|Input file for running PB
|&general
| keep_files=2,
|/
|&pb
| istrng=0.100,
|/
|--------------------------------------------------------------
|MMPBSA.py Version=12.0
|Solvated complex topology file: solvated_complex.prmtop
|Complex topology file: complex.prmtop
|Solvated receptor topology file: solvated_receptor.prmtop
|Receptor topology file: receptor.prmtop
|Solvated ligand topology file: solvated_ligand.prmtop
|Ligand topology file: ligand.prmtop
|Initial mdcrd(s): solvated_complex.mdcrd
|Initial Receptor mdcrd(s): solvated_receptor.mdcrd
|Initial Ligand mdcrd(s): solvated_ligand.mdcrd
|
|Receptor mask: ":1-259,261"
|Ligand mask: ":260"
|Ligand residue name is "GRL"
|
|Calculations performed using 2000 complex frames.
|Poisson Boltzmann calculations performed using internal PBSA solver in
mmpbsa_py_energy mmpbsa_py_energy All units are reported in kcal/mole.
POISSON BOLTZMANN:
Complex:
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
BOND 736.7279 22.0640
0.4934
ANGLE 1995.1998 33.4215 0.7473
DIHED 2678.0345 17.6255
0.3941
VDWAALS -2087.8382 17.0521 0.3813
EEL -18886.2185 45.2532
1.0119
1-4 VDW 939.5232 12.2021 0.2728
1-4 EEL 12018.5597 34.4107 0.7694
EPB -2756.8506 32.0416
0.7165
ENPOLAR 1947.5890 4.0342 0.0902
G gas -2606.0115 52.3234
1.1700
G solv -809.2616 31.0811
0.6950
TOTAL -3415.2731 42.4828
0.9499
Receptor:
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
BOND 730.9340 22.3084
0.4988
ANGLE 1988.9648 34.0877
0.7622
DIHED 2673.3837 17.7613
0.3972
VDWAALS -2069.5571 17.0144 0.3805
EEL -18740.8834 46.1644
1.0323
1-4 VDW 932.4446 12.5577
0.2808
1-4 EEL 12001.3338 35.2803
0.7889
EPB -2843.9385 33.2404
0.7433
ENPOLAR 1927.6929 4.1456 0.0927
G gas -2483.3795 52.8123
1.1809
G solv -916.2456 32.3392
0.7231
TOTAL -3399.6251 45.0321
1.0069
Ligand:
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
BOND 7.1550 2.1795
0.0487
ANGLE 17.2751 2.2993 0.0514
DIHED 6.2944 1.9402
0.0434
VDWAALS -2.8514 0.4370 0.0098
EEL -3.4786 0.6157
0.0138
1-4 VDW 9.3533 0.8495 0.0190
1-4 EEL -0.9066 0.6733
0.0151
EPB -13.4620 0.6149
0.0138
ENPOLAR 29.2639 0.1966 0.0044
G gas 32.8413 3.5696
0.0798
G solv 15.8019 0.7199
0.0161
TOTAL 48.6431 3.5225
0.0788
Differences (Complex - Receptor - Ligand):
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
BOND -1.3611 31.4521
0.7033
ANGLE -11.0401 47.7939 1.0687
DIHED -1.6436 25.0975
0.5612
VDWAALS -15.4297 24.0926 0.5387
EEL -141.8565 64.6482
1.4456
1-4 VDW -2.2748 17.5303
0.3920
1-4 EEL 18.1326 49.2874
1.1021
EPB 100.5499 46.1733
1.0325
ENPOLAR -9.3677 5.7879 0.1294
EDISPER 0.0000 0.0000
0.0000
DELTA G gas -155.4732 74.4286 1.6643
DELTA G solv 91.1822 44.8595
1.0031
DELTA TOTAL -64.2911 62.0088 1.3866
Please let us know if any comment.
Many thanks,
Henry
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Received on Wed Dec 12 2012 - 10:30:02 PST
