Sorry, my mistake, the unit for kb was M-1 (not s-1 which was for kET).
With this correction, I think it would make sense to use the DG
relationship with kb.
On Mon, Apr 19, 2021 at 7:45 PM Adrian Roitberg <roitberg.ufl.edu> wrote:
> 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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> > Birla Institute of Technology and Sciences Pilani (BITS-Pilani),
> > VidyaVihar Campus, street number 41, Pilani, Rajasthan 333031.
> > India.
> > Phone No. +91 1596 255652, Mob. No. +91-7709129400,
> > Email: vaibhav.dixit.pilani.bits-pilani.ac.in, vaibhavadixit.gmail.com
> >
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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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--
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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Birla Institute of Technology and Sciences Pilani (BITS-Pilani),
VidyaVihar Campus, street number 41, Pilani, Rajasthan 333031.
India.
Phone No. +91 1596 255652, Mob. No. +91-7709129400,
Email: vaibhav.dixit.pilani.bits-pilani.ac.in, vaibhavadixit.gmail.com
http://www.bits-pilani.ac.in/pilani/vaibhavdixit/profile
https://www.linkedin.com/in/vaibhav-dixit-b1a07a39/
ORCID ID: https://orcid.org/0000-0003-4015-2941
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Received on Mon Apr 19 2021 - 07:30:04 PDT
