Hi
Just to clarify, kb in units of s^-1 is NOT a measure of affinity. It
could be rate constant, but for sure, it is not anything you would want
to use to do
Delta-G = -RT * ln(kb)
Adrian
On 4/18/21 1:20 PM, Vaibhav Dixit wrote:
> [External Email]
>
> Dear All,
> I'm getting very high entropy values after running the MMPBSA with the
> following input.
> The vibrational contribution seems very large (-ve) number.
> The GBSA based enthalpy looks reasonable since the two proteins are known
> to have a weak binding affinity (kb ~ 700 s-1) at 300 K. I was hoping to
> combine the Delta-H (from GBSA and PBSA) calculations with Delta-S
> calculations to get the total Delta-G and then use Delta-G = -RT * ln(kb)
> to see if it agrees with the experimental data.
>
> Can you please help me understand what might be the problem here?
> It will also help if you can comment on the correctness of my approach here
> and what might be the associated pitfalls. The MMPBSA reference doesn't
> seems to address these aspects.
> Thus valuable insights and comments are highly appreciated.
> Thanks a lot and best regards.
>
> | Run on Mon Apr 19 00:34:17 2021
> |
> |Input file:
> |--------------------------------------------------------------
> |Input file for running nmode and GB
> |&general
> | endframe=2000, verbose=2, interval=5,
> | entropy=1,
> |/
> |&gb
> | igb=5,
> |
> |/
> |
> |--------------------------------------------------------------
> |MMPBSA.py Version=14.0
> |Solvated complex topology file: ../1hga-3ner-solv.prmtop
> |Complex topology file: 1hga-3ner-complex.prmtop
> |Receptor topology file: 1hga-recp1.prmtop
> |Ligand topology file: 3ner-lig1.prmtop
> |Initial mdcrd(s): ../1hga-3ner-solv-prod300-reimaged.nc
> |
> |Receptor mask: ":1-143"
> |Ligand mask: ":144-235"
> |
> |Calculations performed using 400 complex frames.
> |
> |Generalized Born ESURF calculated using 'LCPO' surface areas
> |
> |All units are reported in kcal/mole.
> |All entropy results have units kcal/mol (Temperature is 298.15 K).
> -------------------------------------------------------------------------------
> -------------------------------------------------------------------------------
> ENTROPY RESULTS (QUASI-HARMONIC APPROXIMATION) CALCULATED WITH PTRAJ:
> Translational Rotational Vibrational Total
> Complex: 16.7930 17.5417 888.2178 922.5524
> Receptor: 16.3264 16.4191 744.8073 777.5525
> Ligand: 15.9981 15.9934 736.5319 768.5234
>
> DELTA S: -15.5315 -14.8708 -593.1214 -623.5235
> -------------------------------------------------------------------------------
> -------------------------------------------------------------------------------
>
> GENERALIZED BORN:
>
> Complex:
> Energy Component Average Std. Dev. Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND 844.4563 33.9946
> 1.6997
> ANGLE 2293.4877 33.7218
> 1.6861
> DIHED 1198.4857 18.1241
> 0.9062
> VDWAALS -1734.8917 22.4482
> 1.1224
> EEL -17168.3020 109.5404
> 5.4770
> 1-4 VDW 838.9863 12.0959
> 0.6048
> 1-4 EEL 12041.8362 58.1348
> 2.9067
> EGB -3376.9606 86.3362
> 4.3168
> ESURF 102.4703 1.7543
> 0.0877
>
> G gas -1685.9416 106.9086
> 5.3454
> G solv -3274.4903 85.9813
> 4.2991
>
> TOTAL -4960.4319 48.0756
> 2.4038
>
>
> Receptor:
> Energy Component Average Std. Dev. Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND 416.0058 16.0560
> 0.8028
> ANGLE 1278.9046 25.4859
> 1.2743
> DIHED 688.8077 14.2048
> 0.7102
> VDWAALS -1105.7934 15.2715
> 0.7636
> EEL -10471.9733 71.2250
> 3.5612
> 1-4 VDW 502.2180 9.2879
> 0.4644
> 1-4 EEL 7057.2247 31.7299
> 1.5865
> EGB -1272.0252 58.3189
> 2.9159
> ESURF 54.6697 1.3079
> 0.0654
>
> G gas -1634.6059 73.0947
> 3.6547
> G solv -1217.3554 57.6275
> 2.8814
>
> TOTAL -2851.9613 35.9199
> 1.7960
>
>
> Ligand:
> Energy Component Average Std. Dev. Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND 428.4505 29.8335
> 1.4917
> ANGLE 1014.5831 23.9354
> 1.1968
> DIHED 509.6780 12.6930
> 0.6346
> VDWAALS -618.2028 14.6859
> 0.7343
> EEL -6213.0919 78.1662
> 3.9083
> 1-4 VDW 336.7683 8.0045
> 0.4002
> 1-4 EEL 4984.6115 49.8345
> 2.4917
> EGB -2593.5910 69.7658
> 3.4883
> ESURF 50.4901 1.3869
> 0.0693
>
> G gas 442.7966 73.9919
> 3.6996
> G solv -2543.1009 69.0004
> 3.4500
>
> TOTAL -2100.3043 31.4666
> 1.5733
>
>
> Differences (Complex - Receptor - Ligand):
> Energy Component Average Std. Dev. Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> BOND -0.0000 0.0001
> 0.0000
> ANGLE -0.0000 0.0001
> 0.0000
> DIHED -0.0000 0.0001
> 0.0000
> VDWAALS -10.8955 8.5405
> 0.4270
> EEL -483.2368 81.8501
> 4.0925
> 1-4 VDW 0.0000 0.0001
> 0.0000
> 1-4 EEL -0.0000 0.0000
> 0.0000
> EGB 488.6556 77.8583
> 3.8929
> ESURF -2.6895 1.3187
> 0.0659
>
> DELTA G gas -494.1323 85.3064
> 4.2653
> DELTA G solv 485.9660 76.9182
> 3.8459
>
> DELTA TOTAL -8.1663 10.2147
> 0.5107
>
>
> -------------------------------------------------------------------------------
> -------------------------------------------------------------------------------
> Using Quasi-harmonic Entropy Approximation: DELTA G binding = 615.3572
> -------------------------------------------------------------------------------
> -------------------------------------------------------------------------------
>
> --
>
> Regards,
>
> Dr. Vaibhav A. Dixit,
>
> Visiting Scientist at the Manchester Institute of Biotechnology (MIB), The
> University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
> AND
> Assistant Professor,
> Department of Pharmacy,
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> VidyaVihar Campus, street number 41, Pilani, Rajasthan 333031.
> India.
> Phone No. +91 1596 255652, Mob. No. +91-7709129400,
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--
Dr. Adrian E. Roitberg
V.T. and Louise Jackson Professor in Chemistry
Department of Chemistry
University of Florida
roitberg.ufl.edu
352-392-6972
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Received on Mon Apr 19 2021 - 07:30:03 PDT
