On the ligand, the RMSD that needs to converge is based on the internal
coordinates, not the translation/rotation of the whole molecule, so you
should align the ligand first when doing that kind of analysis. I think
those translations/rotations need to be taken out for the purpose of the
entropy calculation, but not for other things.
I have nothing else of value to offer sadly. but I do recall the manual
being pretty specific about the coordinates and such that it wants, and I
thought for this kind of calculation, it wants the whole complex with water
for the *.prmtop parameter file, and water-stripped coordinate trajectories
for the receptor, ligand, and complex?
~Aron
On Wed, Dec 12, 2012 at 1:00 PM, <psu4.uic.edu> wrote:
> 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
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
Aron Broom M.Sc
PhD Student
Department of Chemistry
University of Waterloo
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Received on Wed Dec 12 2012 - 11:30:01 PST
