Re: [AMBER] Very low MMPBSA result

From: Ray Luo <rluo.uci.edu>
Date: Sun, 12 Apr 2020 09:01:23 -0700

Nadaafiva,

My guess is that your receptor and ligand are bonded. You can't define
them as separate molecules if they are bonded.

All the best,
Ray
--
Ray Luo, Ph.D.
Professor of Structural Biology/Biochemistry/Biophysics,
Chemical and Materials Physics, Chemical and Biomolecular Engineering,
Biomedical Engineering, and Materials Science and Engineering
Department of Molecular Biology and Biochemistry
University of California, Irvine, CA 92697-3900
On Sat, Apr 11, 2020 at 11:11 PM Nada Afiva <nadaafiva.gmail.com> wrote:
>
> Thank you Prof. Case,
> Yes, the bond energy in my calculation is not zero.
> I tried to understand what you suggest, so
> I performed MMPBSA calculation for one frame, and below is the result.
> However, still, I could not figure out what's wrong.
>
> Best regards,
> nadaafiva
>
>
> Result for MMPBSA calculation for one frame
>
> GENERALIZED BORN:
>
> WARNING: INCONSISTENCIES EXIST WITHIN INTERNAL POTENTIAL
> TERMS. THE VALIDITY OF THESE RESULTS ARE HIGHLY QUESTIONABLE
> Complex:
> Energy Component            Average              Std. Dev.   Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND                      4987.7384               14.6855
> 10.3842
> ANGLE                     8783.1966               28.4633
> 20.1266
> DIHED                    14002.0148               27.6907
> 19.5803
> VDWAALS                  -8312.5223               12.0942
>  8.5519
> EEL                     -77073.8675               25.2760
> 17.8729
> 1-4 VDW                   4093.3003                8.0252
>  5.6747
> 1-4 EEL                  41943.1001              123.0514
> 87.0105
> EGB                      -9900.1568               67.0942
> 47.4428
> ESURF                      337.1691                0.0760
>  0.0537
>
> G gas                   -11577.0396               47.0552
> 33.2731
> G solv                   -9562.9878               67.0183
> 47.3891
>
> TOTAL                   -21140.0274               19.9630
> 14.1160
>
>
> Receptor:
> Energy Component            Average              Std. Dev.   Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND                      6474.7614              125.2608
> 88.5727
> ANGLE                     8770.3780               49.1306
> 34.7406
> DIHED                    13973.9255               29.0412
> 20.5352
> VDWAALS                  -8283.8561               16.7430
> 11.8391
> EEL                     -77911.4475               17.1252
> 12.1094
> 1-4 VDW                   4077.8936                8.3679
>  5.9170
> 1-4 EEL                  44003.5112              113.3456
> 80.1475
> EGB                      -9932.5902               66.6209
> 47.1081
> ESURF                      338.7891                0.0463
>  0.0328
>
> G gas                    -8894.8338              168.4202
>  119.0911
> G solv                   -9593.8011               66.6672
> 47.1409
>
> TOTAL                   -18488.6349              101.7530
> 71.9502
>
>
> Ligand:
> Energy Component            Average              Std. Dev.   Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND                        29.2077                4.9909
>  3.5291
> ANGLE                       93.0959                3.4445
>  2.4357
> DIHED                       41.1711                0.9216
>  0.6517
> VDWAALS                     -1.6857                1.1140
>  0.7878
> EEL                        958.3478               11.8859
>  8.4046
> 1-4 VDW                     15.2138                0.3411
>  0.2412
> 1-4 EEL                  -2065.3416                9.6983
>  6.8577
> EGB                        -99.0266                1.5256
>  1.0787
> ESURF                        3.6076                0.0107
>  0.0076
>
> G gas                     -929.9910                4.2675
>  3.0176
> G solv                     -95.4190                1.5362
>  1.0863
>
> TOTAL                    -1025.4100                2.7313
>  1.9313
>
>
> Differences (Complex - Receptor - Ligand):
> Energy Component            Average              Std. Dev.   Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND                     -1516.2308              134.9554
> 95.4279
> ANGLE                      -80.2772               17.2227
> 12.1783
> DIHED                      -13.0818                0.4289
>  0.3033
> VDWAALS                    -26.9805                3.5347
>  2.4994
> EEL                       -120.7679                3.7351
>  2.6411
> 1-4 VDW                      0.1928                0.0016
>  0.0011
> 1-4 EEL                      4.9305                0.0075
>  0.0053
> EGB                        131.4599                1.9989
>  1.4134
> ESURF                       -5.2275                0.1116
>  0.0789
>
> DELTA G gas              -1752.2148              117.0974
> 82.8004
> DELTA G solv               126.2324                1.8873
>  1.3345
>
> DELTA TOTAL              -1625.9825              118.9847
> 84.1349
>
>
> -------------------------------------------------------------------------------
> -------------------------------------------------------------------------------
>
> POISSON BOLTZMANN:
>
> WARNING: INCONSISTENCIES EXIST WITHIN INTERNAL POTENTIAL
> TERMS. THE VALIDITY OF THESE RESULTS ARE HIGHLY QUESTIONABLE
> Complex:
> Energy Component            Average              Std. Dev.   Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND                      4987.7384               14.6855
> 10.3842
> ANGLE                     8783.1966               28.4633
> 20.1266
> DIHED                    14002.0148               27.6907
> 19.5803
> VDWAALS                  -8312.5223               12.0942
>  8.5519
> EEL                     -77073.8675               25.2760
> 17.8729
> 1-4 VDW                   4093.3003                8.0252
>  5.6747
> 1-4 EEL                  41943.1001              123.0514
> 87.0105
> EPB                     -11008.9913               57.7731
> 40.8518
> ENPOLAR                    221.0373                0.3891
>  0.2752
>
> G gas                   -11577.0396               47.0552
> 33.2731
> G solv                  -10787.9541               58.1622
> 41.1269
>
> TOTAL                   -22364.9937               11.1070
>  7.8538
>
>
> Receptor:
> Energy Component            Average              Std. Dev.   Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND                      6474.7614              125.2608
> 88.5727
> ANGLE                     8770.3780               49.1306
> 34.7406
> DIHED                    13973.9255               29.0412
> 20.5352
> VDWAALS                  -8283.8561               16.7430
> 11.8391
> EEL                     -77911.4475               17.1252
> 12.1094
> 1-4 VDW                   4077.8936                8.3679
>  5.9170
> 1-4 EEL                  44003.5112              113.3456
> 80.1475
> EPB                     -11026.8306               58.4378
> 41.3218
> ENPOLAR                    221.6744                0.4101
>  0.2900
>
> G gas                    -8894.8338              168.4202
>  119.0911
> G solv                  -10805.1563               58.8480
> 41.6118
>
> TOTAL                   -19699.9901              109.5722
> 77.4792
>
>
> Ligand:
> Energy Component            Average              Std. Dev.   Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND                        29.2077                4.9909
>  3.5291
> ANGLE                       93.0959                3.4445
>  2.4357
> DIHED                       41.1711                0.9216
>  0.6517
> VDWAALS                     -1.6857                1.1140
>  0.7878
> EEL                        958.3478               11.8859
>  8.4046
> 1-4 VDW                     15.2138                0.3411
>  0.2412
> 1-4 EEL                  -2065.3416                9.6983
>  6.8577
> EPB                       -113.2438                1.5723
>  1.1118
> ENPOLAR                      3.2812                0.0092
>  0.0065
>
> G gas                     -929.9910                4.2675
>  3.0176
> G solv                    -109.9625                1.5632
>  1.1053
>
> TOTAL                    -1039.9536                2.7043
>  1.9123
>
>
> Differences (Complex - Receptor - Ligand):
> Energy Component            Average              Std. Dev.   Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND                     -1516.2308              134.9554
> 95.4279
> ANGLE                      -80.2772               17.2227
> 12.1783
> DIHED                      -13.0818                0.4289
>  0.3033
> VDWAALS                    -26.9805                3.5347
>  2.4994
> EEL                       -120.7679                3.7351
>  2.6411
> 1-4 VDW                      0.1928                0.0016
>  0.0011
> 1-4 EEL                      4.9305                0.0075
>  0.0053
> EPB                        131.0832                0.9076
>  0.6417
> ENPOLAR                     -3.9183                0.0301
>  0.0213
> EDISPER                      0.0000                0.0000
>  0.0000
>
> DELTA G gas              -1752.2148              117.0974
> 82.8004
> DELTA G solv               127.1648                0.8774
>  0.6204
>
> DELTA TOTAL              -1625.0500              117.9748
> 83.4208
>
> Pada tanggal Sab, 11 Apr 2020 pukul 19.00 David A Case <
> david.case.rutgers.edu> menulis:
>
> > On Sat, Apr 11, 2020, Nada Afiva wrote:
> >
> > >Yes I am using the single-trajectory approach.
> >
> > If you use the single-trajectory approach, then the bond energy
> > contribution to binding should be zero.  Try a very short simlation,
> > even one frame: since you have saved the intermediate files, just do a
> > single-step calculation (by hand) on receptor, ligand and complex, and
> > do the delta calculations yourself.  You may be able to see what is
> > going wrong.
> >
> > ....dac
> >
> >
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
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Received on Sun Apr 12 2020 - 09:30:02 PDT
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