On Thu, 2014-04-24 at 08:38 +0530, Arunima Shilpi wrote:
> Dear Sir
>
> Here while detlta G by MMPBSA for protein-ligand complex I am geting the
> positive for delta G. Here one of the residue C1191 has been mutated to
> C1191I and then the delta G binding have been calculated.
>
> Here are the details of input command and the Final results
>
> #!/bin/sh
> #PBS -N C1191K_3781_r
> #PBS -l select=1:ncpus=8
> #PBS -j oe
> #PBS -q small
>
> cd $PBS_O_WORKDIR > pwd
> cat $PBS_NODEFILE > pbsnodes
>
> /opt/intel/impi/4.1.0.024/intel64/bin/mpirun -machinefile $PBS_NODEFILE -np
> 8 $AMBERHOME/bin/MMPBSA.py.MPI -O -i mmpbsa.in -o FINAL_RESULTS_MMPBSA.dat
> -sp C1191K_DRG_solvated.prmtop -cp C1191K_DRG.prmtop -rp C1191K.prmtop -lp
> DRG.prmtop -y *.mdcrd
>
>
> and final results is
>
[snip]
> Differences (Complex - Receptor - Ligand):
> Energy Component Average Std. Dev. Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> VDWAALS -59.7408 3.9526
> 0.5590
> EEL -67.1741 7.3094
> 1.0337
> EGB 87.3878 6.1042
> 0.8633
> ESURF -8.1986 0.2427
> 0.0343
>
> DELTA G gas -126.9150 7.4496
> 1.0535
> DELTA G solv 79.1893 6.0356
> 0.8536
>
> DELTA TOTAL -47.7257 3.3376
> 0.4720
>
>
> -------------------------------------------------------------------------------
> -------------------------------------------------------------------------------
>
> POISSON BOLTZMANN:
[snip]
> Differences (Complex - Receptor - Ligand):
> Energy Component Average Std. Dev. Std. Err. of
> Mean
> -------------------------------------------------------------------------------
> VDWAALS -59.7408 3.9526
> 0.5590
> EEL -67.1741 7.3094
> 1.0337
> EPB 101.1607 7.3105
> 1.0339
> ENPOLAR -41.3671 1.2286
> 0.1737
> EDISPER 76.0735 1.3057
> 0.1846
>
> DELTA G gas -126.9150 7.4496
> 1.0535
> DELTA G solv 135.8671 7.3979
> 1.0462
>
> DELTA TOTAL 8.9521 5.0649
> 0.7163
>
>
> -------------------------------------------------------------------------------
> -------------------------------------------------------------------------------
>
>
> I request you yo kindly guide me in debugging the error.
There is no error. The calculation finished correctly and did what you
told it to do. The main difference between the GB and PB results lies
in the fact that the nonpolar solvation model used by PB is a more
destabilizing model than the simple, linear SASA-based model used by GB.
You can use the "inp=1" variable in the &pb namelist to use a similar
model for PB nonpolar energies if you want to.
It's important to understand what MM/GBSA and MM/PBSA calculations can
and cannot do. Despite the fact that MMPBSA.py is (somewhat) easy to
use, MM/PBSA calculations should be considered advanced (indeed, the
tutorial is in the "advanced" section of our tutorial list) and you
should understand the underlying theory behind the methods you are
using.
Specifically, MM/PBSA calculations are typically bad for predicting
absolute binding free energies, so only energy differences really
matter. The polar solvation energies are typically pretty good, but the
nonpolar solvation models are over-simplified in my opinion and in
general unreliable for absolute energy predictions. The simple
SASA-based model (inp=1) has worked fine in the studies I've seen, but I
haven't looked into the new dispersion/cavitation model used by PBSA
much so I can't comment on how well it works in general. The manual
should contain helpful citations that I would suggest reading to get a
better understanding of the model's strengths and weaknesses (the
citation should be present where the "inp" variable is described).
Good luck,
Jason
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Thu Apr 24 2014 - 04:30:02 PDT
