Hi Giulia,
Here are the answers in red ink
By using the GENERALIZED BORN approximation, I get a final Delta
Energy of *49.3378
*kcal/mol. Whereas, by using the POISSON BOLTZMANN approximation, I get a
final Delta Energy of *254.6772* kcal/mol/.
>>> I don't see anything suspicious here considering that you are working with protein-protein interactions and such high values can be expected. However, these values have no meaning in an absolute sense. Had you changed you ligand and then compared the two GB and PB values you would have gotten an idea about which of them was a better at binding to the receptor. Have you considered the entropy component of binding?? Otherwise, these values are just the enthalpy of binding and not the "deltaG(binding)". Moreover, a lot depends on what atomic radii you have used (for ex. mbondi2, mbondi3.......) and also on what internal dielectric constant you are using. Refer to these papers to get more insights into how various tunable parameters play a role in the accuracy and reliability of MM-PBSA and MM-GBSA calculations.
http://pubs.acs.org/doi/abs/10.1021/ci100275a
http://pubs.rsc.org/-/content/articlelanding/2014/cp/c4cp01388c#!divAbstract
http://pubs.acs.org/doi/abs/10.1021/jp404160y
http://pubs.rsc.org/is/content/articlelanding/2016/cp/c6cp03670h#!divAbstract
Moreover, for GB calculations you can consider using various GB models [for ex. igb = 1, 2, 5 and 8 (ambertools 16 and above)]
I would like to ask you if these energies are realistic considering the
size and characteristics of my system, which are the following: I am
dealing with an RNA dimer, composed of a total of 3219 atoms (2153 for the
first monomer, considered as "receptor" and 1066 atoms for the second
monomer, considered as "ligand"). The original system includes Mg2+ ions
(co-crystallized) and Na+ ions (used as counterions to balance the charge
of the system). For the MMPBSA calculation, I have deleted the ions and
considered the dry receptor, the dry ligand and the dry complex.
>> It would be very difficult to comment on how realistic these values are unless you have some validation sets. Refer to these papers and it will guide you through
http://www.sciencedirect.com/science/article/pii/S0022283603006107
http://onlinelibrary.wiley.com/doi/10.1002/jcc.10379/full
I see from the post in the mailing list (
http://archive.ambermd.org/201208/0072.html) that they get unreasonable
results and that a reasonable value must be of the order of *-200
*kcal/mol *(negative
energy) .*
>> I am afraid I cannot comment anything on that results.
Can you please advise me on that?
There is something I am doing wrong in the set-up of the system?
>> I don't see anything wrong in your setup from what you have written.
Shell I include the ions in the MMPBSA calculation?? And if so, would the
MMPBSA method still be valid?
>> NO, the mobile ions added for the sake of neutralising the systems needs to be deleted and you have correctly followed this.
I hope this helps.
Best Regards
[photo]
Elvis Martis
PhD Student (Computational Chemistry)
at Bombay College of Pharmacy
A Kalina, Santacruz [E], Mumbai 400098, INDIA
W www.elvismartis.in<
https://webapp.wisestamp.com/www.elvismartis.in>
Skype. adrian_elvis12<
https://webapp.wisestamp.com/#>
[
https://ci3.googleusercontent.com/proxy/P0F8-p0kwxKdscp6zsT-ZSRttk9OJEsBGiaXej_H2ERz8n2ma5SLHFAWJdKL-wqOlXSGjbmEyga9C8lmU1bs-_yPIq3CnazA5eJVDYjce1r-34uwxqjjRnmAtE473lEq28nSHQ=s0-d-e1-ft#https://s3.amazonaws.com/images.wisestamp.com/icons_for_colors_32/linkedin.png]<
http://www.linkedin.com/in/elvisadrianmartis/>
________________________________
From: giulia palermo <giulia.palermo83.gmail.com>
Sent: 27 June 2017 23:23:06
To: AMBER Mailing List
Subject: Re: [AMBER] error running mmpbsa
Dear Elvis,
by including these keywords in the following input file (see below), I have
been able to compete the calculations.
However, I have a very important question related to the computed energies.
By using the GENERALIZED BORN approximation, I get a final Delta
Energy of *49.3378
*kcal/mol. Whereas, by using the POISSON BOLTZMANN approximation, I get a
final Delta Energy of *254.6772* kcal/mol/.
I would like to ask you if these energies are realistic considering the
size and characteristics of my system, which are the following: I am
dealing with an RNA dimer, composed of a total of 3219 atoms (2153 for the
first monomer, considered as "receptor" and 1066 atoms for the second
monomer, considered as "ligand"). The original system includes Mg2+ ions
(co-crystallized) and Na+ ions (used as counterions to balance the charge
of the system). For the MMPBSA calculation, I have deleted the ions and
considered the dry receptor, the dry ligand and the dry complex.
I see from the post in the mailing list (
http://archive.ambermd.org/201208/0072.html) that they get unreasonable
results and that a reasonable value must be of the order of *-200
*kcal/mol *(negative
energy) .*
Can you please advise me on that?
There is something I am doing wrong in the set-up of the system?
Shell I include the ions in the MMPBSA calculation?? And if so, would the
MMPBSA method still be valid?
Thank you very much
Giulia
&general
endframe=200, keep_files=2, interval=10,
/
&gb
igb=2, saltcon=0.100,
/
&pb
istrng=0.100, inp=1, radiopt=0,
/
2017-06-26 18:18 GMT-07:00 Elvis Martis <elvis.martis.bcp.edu.in>:
> HI,
>
> Here PB radii set couldn't find parameters for 3 C5'Cl* not very difficult
> to work around this one.
>
> There is an older post here which will help you solve the problem
> http://archive.ambermd.org/201303/0550.html
>
> Re: [AMBER] PB Bomb in pb_aaradi(): No radius assigned for ...<
> http://archive.ambermd.org/201303/0550.html>
> archive.ambermd.org
> From: Xioling Chuang Date: Thu, 28 Mar 2013 16:56:21 +0100 Dear Jason,
> Thank you very much for your help. It works fine with setting inp=1 and ...
>
>
>
>
> Best Regards
>
> [photo]
>
>
>
> Elvis Martis
> Ph.D. Student (Computational Chemistry)
> at Bombay College of Pharmacy
>
>
> A Kalina, Santacruz [E], Mumbai 400098, INDIA
> W www.elvismartis.in<https://webapp.wisestamp.com/www.elvismartis.in>
> Skype. adrian_elvis12<https://webapp.wisestamp.com/#>
>
>
> [https://ci3.googleusercontent.com/proxy/P0F8-p0kwxKdscp6zsT-
> ZSRttk9OJEsBGiaXej_H2ERz8n2ma5SLHFAWJdKL-wqOlXSGjbmEyga9C8lmU1bs-_
> yPIq3CnazA5eJVDYjce1r-34uwxqjjRnmAtE473lEq28nSHQ=s0-
> d-e1-ft#https://s3.amazonaws.com/images.wisestamp.com/
> icons_for_colors_32/linkedin.png]<http://www.linkedin.com/
> in/elvisadrianmartis/>
>
>
>
>
>
> ________________________________
> From: giulia palermo <giulia.palermo83.gmail.com>
> Sent: 27 June 2017 05:23:59
> To: AMBER Mailing List
> Subject: Re: [AMBER] error running mmpbsa
>
> Dear Elvis,
>
> thank you very much for these useful information. I have checked all files
> and it seems that one of the problems was the fact that the trajectory was
> in mdcrd format. Using the netcdf format, it seems making at least the GB
> calculation.
>
> This is now my command line:
>
> MMPBSA.py -O -i mmpbsa.in -o FINAL_RESULTS_MMPBSA.dat -cp tutto.top -rp
> azzurro.top -lp rosa.top -y tutto.nc
>
> Let me give you some more information about my system. I am dealing with an
> RNA dimer and I want to calculate the binding energy between the two
> monomers. As such, I am treating one monomer (the bigger) as the receptor
> (azzurro.top), while the other monomeris treated as the ligand (rosa.top).
> I have carefully checked that the number of atoms in the azzurro.top + the
> number of atoms in the rosa.top equals the total number of atoms in the
> topology and in the trajectory of the complex (tutto.top and tutto.nc).
>
> However, as you can see below, I still have problems that seem to be
> related to the fact that there is *No radius assigned for atom 3 C5'
> CI*
>
> Do you have some insights on how to overcome this issue?
>
>
> Thank you very much
> Giulia
>
>
>
>
>
>
> Loading and checking parameter files for compatibility...
> mmpbsa_py_energy found! Using
> /net/software/pkg/amber/amber14-test/bin/mmpbsa_py_energy
> cpptraj found! Using /net/software/pkg/amber/amber14-test/bin/cpptraj
> Preparing trajectories for simulation...
> 20 frames were processed by cpptraj for use in calculation.
>
> Running calculations on normal system...
>
> Beginning GB calculations with
> /net/software/pkg/amber/amber14-test/bin/mmpbsa_py_energy
> calculating complex contribution...
> calculating receptor contribution...
> calculating ligand contribution...
>
> Beginning PB calculations with
> /net/software/pkg/amber/amber14-test/bin/mmpbsa_py_energy
> calculating complex contribution...
> File "/net/software/pkg/amber/amber14-test/bin/MMPBSA.py", line 104, in
> <module>
> app.run_mmpbsa()
> File
> "/net/software/pkg/amber/amber14-test/lib/python2.7/
> site-packages/MMPBSA_mods/main.py",
> line 218, in run_mmpbsa
> self.calc_list.run(rank, self.stdout)
> File
> "/net/software/pkg/amber/amber14-test/lib/python2.7/
> site-packages/MMPBSA_mods/calculation.py",
> line 82, in run
> calc.run(rank, stdout=stdout, stderr=stderr)
> File
> "/net/software/pkg/amber/amber14-test/lib/python2.7/
> site-packages/MMPBSA_mods/calculation.py",
> line 431, in run
> self.prmtop) + '\n\t'.join(error_list) + '\n')
>
> *CalcError: /net/software/pkg/amber/amber14-test/bin/mmpbsa_py_energy
> failed with prmtop tutto.top! PB Bomb in pb_aaradi(): No radius assigned
> for atom 3 C5' CI*
>
> Exiting. All files have been retained.
>
>
>
> 2017-06-24 20:35 GMT-07:00 Elvis Martis <elvis.martis.bcp.edu.in>:
>
> > Hi,
> >
> > one quick question why are your directory names starting with 0??? try
> > renaming the directory to start with a letter and number can be pushed at
> > the end.
> >
> > Did you also check that all top files are OK?
> >
> > the number of atoms in receptor top + ligand top should be equal to
> > complex top file and the trajectory file.
> >
> > Error: Third line contains invalid atom index. >>>>> Check your top file
> > for this
> > Error: -17.043Error: Could not set up tutto.mdcrd for reading. >>>
> > http://archive.ambermd.org/201306/0241.html
> >
> > Error: Could not set up input trajectory 'tutto.mdcrd'. >>>
> > http://archive.ambermd.org/201306/0241.html
> >
> >
> > Hope this helps
> >
> >
> > Best Regards
> >
> > [photo]
> >
> >
> >
> > Elvis Martis
> > Ph.D. Student (Computational Chemistry)
> > at Bombay College of Pharmacy
> >
> >
> > A Kalina, Santacruz [E], Mumbai 400098, INDIA
> > W www.elvismartis.in<https://webapp.wisestamp.com/www.elvismartis.in>
> > Skype. adrian_elvis12<https://webapp.wisestamp.com/#>
> >
> >
> > [https://ci3.googleusercontent.com/proxy/P0F8-p0kwxKdscp6zsT-
> > ZSRttk9OJEsBGiaXej_H2ERz8n2ma5SLHFAWJdKL-wqOlXSGjbmEyga9C8lmU1bs-_
> > yPIq3CnazA5eJVDYjce1r-34uwxqjjRnmAtE473lEq28nSHQ=s0-
> > d-e1-ft#https://s3.amazonaws.com/images.wisestamp.com/
> > icons_for_colors_32/linkedin.png]<http://www.linkedin.com/
> > in/elvisadrianmartis/>
> >
> >
> >
> >
> >
> > ________________________________
> > From: giulia palermo <giulia.palermo83.gmail.com>
> > Sent: 24 June 2017 23:26:40
> > To: AMBER Mailing List
> > Subject: Re: [AMBER] error running mmpbsa
> >
> > Hi Elvis,
> >
> > I have tried the MMPBSA calculations with different amber versions and
> > sourcing he script, lihe this:
> >
> > module load amber/14
> > source /net/software/src/amber/amber14/amber.sh
> >
> > MMPBSA.py -O -i mmpbsa.in -o FINAL_RESULTS_MMPBSA.dat -cp
> > ./0_make_tutto/tutto.top -rp ./0_make_azzurro/azzurro.top -lp
> > ./0_make_rosa/rosa.top -y tutto.mdcrd
> >
> > tutto.mdcrd is the trajetory including receptor and ligand. This
> trajectory
> > is not solvated.
> > I have checked this trajectory and it is compatible with the prmtop file
> > (tutto.top).
> >
> > However, I get the following error (with all AMBER versions I used),
> which
> > is related to the fact that cpptraj can not query tutto.mdcrd. Can you
> > please give me some advice on what is going on?
> > I also report below my MMPBSA input file.
> >
> > Thank you
> > Giulia
> >
> >
> >
> > ---- ERROR :
> > Loading and checking parameter files for compatibility...
> > mmpbsa_py_energy found! Using
> > /net/software/src/amber/amber14/bin/mmpbsa_py_energy
> > cpptraj found! Using /net/software/src/amber/amber14/bin/cpptraj
> > Preparing trajectories for simulation...
> > Error: Third line contains invalid atom index.
> > Error: -17.043Error: Could not set up tutto.mdcrd for reading.
> > Error: Could not set up input trajectory 'tutto.mdcrd'.
> > File "/net/software/src/amber/amber14/bin/MMPBSA.py", line 103, in
> > <module>
> > app.file_setup()
> > File
> > "/net/software/src/amber/amber14/lib/python2.7/site-
> > packages/MMPBSA_mods/main.py",
> > line 156, in file_setup
> > self.mpi_size, str(external_progs['cpptraj']), self.pre)
> > File
> > "/net/software/src/amber/amber14/lib/python2.7/site-
> > packages/MMPBSA_mods/make_trajs.py",
> > line 66, in make_trajectories
> > traj = Trajectory(FILES.complex_prmtop, FILES.mdcrd, cpptraj)
> > File
> > "/net/software/src/amber/amber14/lib/python2.7/site-
> > packages/MMPBSA_mods/make_trajs.py",
> > line 467, in __init__
> > self.Query()
> > File
> > "/net/software/src/amber/amber14/lib/python2.7/site-
> > packages/MMPBSA_mods/make_trajs.py",
> > line 602, in Query
> > raise TrajError('%s failed when querying %s' % (self.exe, traj))
> > *TrajError: /net/software/src/amber/amber14/bin/cpptraj failed when
> > querying tutto.mdcrd*
> > Exiting. All files have been retained.
> >
> >
> > ---- MMPBSA input file
> >
> > &general
> > endframe=200, keep_files=2, interval=10,
> > /
> > &gb
> > igb=2, saltcon=0.100,
> > /
> > &pb
> > istrng=0.100,
> > /
> >
> >
> >
> > 2017-06-23 20:43 GMT-07:00 Elvis Martis <elvis.martis.bcp.edu.in>:
> >
> > > Sorry,
> > >
> > > I meant without quotes
> > >
> > >
> > > Best Regards
> > >
> > > [photo]
> > >
> > >
> > >
> > > Elvis Martis
> > > Ph.D. Student (Computational Chemistry)
> > > at Bombay College of Pharmacy
> > >
> > >
> > > A Kalina, Santacruz [E], Mumbai 400098, INDIA
> > > W www.elvismartis.in<https://webapp.wisestamp.com/www.elvismartis.in>
> > > Skype. adrian_elvis12<https://webapp.wisestamp.com/#>
> > >
> > >
> > > [https://ci3.googleusercontent.com/proxy/P0F8-p0kwxKdscp6zsT-
> > > ZSRttk9OJEsBGiaXej_H2ERz8n2ma5SLHFAWJdKL-wqOlXSGjbmEyga9C8lmU1bs-_
> > > yPIq3CnazA5eJVDYjce1r-34uwxqjjRnmAtE473lEq28nSHQ=s0-
> > > d-e1-ft#https://s3.amazonaws.com/images.wisestamp.com/
> > > icons_for_colors_32/linkedin.png]<http://www.linkedin.com/
> > > in/elvisadrianmartis/>
> > >
> > >
> > >
> > >
> > >
> > > ________________________________
> > > From: Elvis Martis <elvis.martis.bcp.edu.in>
> > > Sent: 24 June 2017 06:39:56
> > > To: AMBER Mailing List
> > > Subject: Re: [AMBER] error running mmpbsa
> > >
> > > HI,
> > >
> > > Try this command before you run you mm_pbsa.py
> > >
> > > "source <path_to_amber_home>/amber.sh" for bash with quotes
> > >
> > > or
> > >
> > > "source <path_to_amber_home>/amber.csh" for csh with quotes
> > >
> > >
> > > Best Regards
> > >
> > > [photo]
> > >
> > >
> > >
> > > Elvis Martis
> > > Ph.D. Student (Computational Chemistry)
> > > at Bombay College of Pharmacy
> > >
> > >
> > > A Kalina, Santacruz [E], Mumbai 400098, INDIA
> > > W www.elvismartis.in<https://webapp.wisestamp.com/www.elvismartis.in>
> > > Skype. adrian_elvis12<https://webapp.wisestamp.com/#>
> > >
> > >
> > > [https://ci3.googleusercontent.com/proxy/P0F8-p0kwxKdscp6zsT-
> > > ZSRttk9OJEsBGiaXej_H2ERz8n2ma5SLHFAWJdKL-wqOlXSGjbmEyga9C8lmU1bs-_
> > > yPIq3CnazA5eJVDYjce1r-34uwxqjjRnmAtE473lEq28nSHQ=s0-
> > > d-e1-ft#https://s3.amazonaws.com/images.wisestamp.com/
> > > icons_for_colors_32/linkedin.png]<http://www.linkedin.com/
> > > in/elvisadrianmartis/>
> > >
> > >
> > >
> > >
> > >
> > > ________________________________
> > > From: giulia palermo <giulia.palermo83.gmail.com>
> > > Sent: 24 June 2017 02:02:54
> > > To: AMBER Mailing List
> > > Subject: [AMBER] error running mmpbsa
> > >
> > > Dear all,
> > >
> > > I am doing some MMPBSA calculations using the dollowing input and
> command
> > > line:
> > >
> > > --- mmpbsa.inp
> > > &general
> > > endframe=2201, keep_files=2, interval=6,
> > > /
> > > &gb
> > > igb=2, saltcon=0.100,
> > > /
> > > &pb
> > > istrng=0.100,
> > > /
> > >
> > > --- command line
> > > MMPBSA.py -O -i mmpbsa.in -o FINAL_RESULTS_MMPBSA.dat -cp
> > > ./0_make_tutto/tutto.top -rp ./0_make_azzurro/azzurro.top -lp
> > > ./0_make_rosa/rosa.top -y tutto.mdcrd
> > >
> > > However, the calculation crashes and I am having the following error:
> > >
> > > Loading and checking parameter files for compatibility...
> > > mmpbsa_py_energy found! Using
> > > /net/software/pkg/amber/amber14-test/bin/mmpbsa_py_energy
> > > cpptraj found! Using /net/software/pkg/amber/amber14-test/bin/cpptraj
> > > Preparing trajectories for simulation...
> > > Error: Third line contains invalid atom index.
> > >
> > > *Error: -17.043Error: Could not set up tutto.mdcrd for reading.Error:
> > > Could not set up input trajectory 'tutto.mdcrd'.*
> > > File "/net/software/pkg/amber/amber14-test/bin/MMPBSA.py", line 103,
> > in
> > > <module>
> > > app.file_setup()
> > > File
> > > "/net/software/pkg/amber/amber14-test/lib/python2.7/
> > > site-packages/MMPBSA_mods/main.py",
> > > line 156, in file_setup
> > > self.mpi_size, str(external_progs['cpptraj']), self.pre)
> > > File
> > > "/net/software/pkg/amber/amber14-test/lib/python2.7/
> > > site-packages/MMPBSA_mods/make_trajs.py",
> > > line 66, in make_trajectories
> > > traj = Trajectory(FILES.complex_prmtop, FILES.mdcrd, cpptraj)
> > > File
> > > "/net/software/pkg/amber/amber14-test/lib/python2.7/
> > > site-packages/MMPBSA_mods/make_trajs.py",
> > > line 467, in __init__
> > > self.Query()
> > > File
> > > "/net/software/pkg/amber/amber14-test/lib/python2.7/
> > > site-packages/MMPBSA_mods/make_trajs.py",
> > > line 602, in Query
> > > raise TrajError('%s failed when querying %s' % (self.exe, traj))
> > > TrajError: /net/software/pkg/amber/amber14-test/bin/cpptraj failed
> when
> > > querying tutto.mdcrd
> > > Exiting. All files have been retained.
> > >
> > >
> > > I have successfully preformed MMPBSA calculations in the past and I can
> > not
> > > understand what is gouing wrong.
> > > It seems that it can not read the trajectory of the complex. But I have
> > > checked it and it seems OK.
> > > Do you have any idea?
> > >
> > > thank you
> > >
> > > Giulia
> > > _______________________________________________
> > > AMBER mailing list
> > > AMBER.ambermd.org
> > > http://lists.ambermd.org/mailman/listinfo/amber
> > > _______________________________________________
> > > AMBER mailing list
> > > AMBER.ambermd.org
> > > http://lists.ambermd.org/mailman/listinfo/amber
> > > _______________________________________________
> > > AMBER mailing list
> > > AMBER.ambermd.org
> > > http://lists.ambermd.org/mailman/listinfo/amber
> > >
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
> _______________________________________________
> AMBER mailing list
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> _______________________________________________
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>
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Received on Tue Jun 27 2017 - 21:30:04 PDT
