Re: [AMBER] controversy in PBSA and GBSA results

From: <h_sahakyan.mb.sci.am> Date: Thu, 01 Oct 2020 06:32:19 +0000

-- 
Harutyun Sahakyan
Senior Assistant at Laboratory of
Computational Modeling of Biological Processes,
Institute of Molecular Biology, NAS RA
7 Hasratyan St, Yerevan, Armenia
Tel: +374 93 323990
E-mail: h_sahakyan.mb.sci.am
October 1, 2020 9:10 AM, "Ray Luo" <rluo.uci.edu> wrote:
> Harutyun,
> 
> Please share your mmpbsa energy outputs, not your MD output.
> 
> 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 Wed, Sep 30, 2020 at 9:17 PM <h_sahakyan.mb.sci.am> wrote:
> 
>> Hi Ray,
>> 
>> Thank you for your reply
>> I used Amber18/AmberTools18.
>> 
>> The final system parameters are:
>> 
>> NSTEP = 49990000 TIME(PS) = 111980.000 TEMP(K) = 309.04 PRESS = 0.0
>> Etot = -264550.3893 EKtot = 68926.3047 EPtot = -333476.6940
>> BOND = 2659.8247 ANGLE = 7371.0874 DIHED = 11181.7492
>> 1-4 NB = 3195.8521 1-4 EEL = 32048.3876 VDWAALS = 36214.6452
>> EELEC = -426148.2401 EHBOND = 0.0000 RESTRAINT = 0.0000
>> EKCMT = 0.0000 VIRIAL = 0.0000 VOLUME = 1091009.1860
>> Density = 1.0239
>> 
>> And here is the input file used for the production:
>> 
>> prod
>> &cntrl
>> imin=0,
>> irest=1,
>> ntx=5,
>> nstlim=50000000,
>> dt=0.002,
>> ntc=2,
>> ntf=2,
>> tol=0.00001,
>> cut=10.0,
>> ntb=2,
>> ntp=1,
>> taup=2.0,
>> ntpr=10000,
>> ntwx=10000,
>> ntwr = 10000,
>> ntwe = 10000,
>> iwrap=1,
>> ntt=3,
>> barostat=2,
>> gamma_ln=2.0,
>> temp0=310.15,
>> tempi=310.15,
>> ig=-1,
>> /
>> 
>> Best regards,
>> Harutyun
>> 
>> -------- Forwarded message -------
>> From: "Ray Luo" <rluo.uci.edu>
>> To: "AMBER Mailing List" <amber.ambermd.org>
>> Sent: October 1, 2020 2:57 AM
>> Subject: Re: [AMBER] controversy in PBSA and GBSA results
>> Harutyun,
>> 
>> Which version of Amber are you using? Also, it's better for us to see
>> your detailed energy output ...
>> 
>> 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 Wed, Sep 30, 2020 at 4:44 AM <h_sahakyan.mb.sci.am> wrote:
>> 
>> Dear All,
>> 
>> I used MM-PBSA/GBSA methods to calculate the binding free energy between two subunits of a protein.
>> The binding energies were -101 and -94 kcal/mol for GBSA and PBSA respectively. However, in the
>> presents of a ligand (between two subunits), binding energies were -124/-67 (GBSA/PBSA). As you can
>> see, according to GBSA the ligand makes the interaction stronger and vice versa according to the
>> PBSA calculation. What can be the reason for this controversy?
>> 
>> I used MMPBSA.py with following input:
>> 
>> pbsa_gbsa
>> &general
>> startframe=1, interval=50, endframe=5000,
>> verbose=2, keep_files=0, netcdf=0,
>> strip_mask = ":WAT,Cl-,Na+,K+,",
>> ligand_mask = ":1-437,867,869",
>> receptor_mask = ":438-865,866,868,870",
>> /
>> &gb
>> saltcon=0.150,
>> /
>> &pb
>> inp=1 # I tried inp=2 it gives more weird results, generally with positive energy values
>> istrng=0.150
>> /
>> Best wishes,
>> Harutyun
>> Senior Assistant at Laboratory of
>> Computational Modeling of Biological Processes,
>> Institute of Molecular Biology, NAS RA
>> 7 Hasratyan St, Yerevan, Armenia
>> Tel: +374 93 323990
>> E-mail: h_sahakyan.mb.sci.am (h_sahakyan.mb.sci.am)
>> _______________________________________________
>> 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
>> 
>> --
>> Senior Assistant at Laboratory of
>> Computational Modeling of Biological Processes,
>> Institute of Molecular Biology, NAS RA
>> 7 Hasratyan St, Yerevan, Armenia
>> Tel: +374 93 323990
>> E-mail: h_sahakyan.mb.sci.am
>> 
>> October 1, 2020 2:57 AM, "Ray Luo" <rluo.uci.edu> wrote:
>> 
>> Harutyun,
>> 
>> Which version of Amber are you using? Also, it's better for us to see
>> your detailed energy output ...
>> 
>> 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 Wed, Sep 30, 2020 at 4:44 AM <h_sahakyan.mb.sci.am> wrote:
>> 
>> Dear All,
>> 
>> I used MM-PBSA/GBSA methods to calculate the binding free energy between two subunits of a protein.
>> The binding energies were -101 and -94 kcal/mol for GBSA and PBSA respectively. However, in the
>> presents of a ligand (between two subunits), binding energies were -124/-67 (GBSA/PBSA). As you can
>> see, according to GBSA the ligand makes the interaction stronger and vice versa according to the
>> PBSA calculation. What can be the reason for this controversy?
>> 
>> I used MMPBSA.py with following input:
>> 
>> pbsa_gbsa
>> &general
>> startframe=1, interval=50, endframe=5000,
>> verbose=2, keep_files=0, netcdf=0,
>> strip_mask = ":WAT,Cl-,Na+,K+,",
>> ligand_mask = ":1-437,867,869",
>> receptor_mask = ":438-865,866,868,870",
>> /
>> &gb
>> saltcon=0.150,
>> /
>> &pb
>> inp=1 # I tried inp=2 it gives more weird results, generally with positive energy values
>> istrng=0.150
>> /
>> Best wishes,
>> Harutyun
>> Senior Assistant at Laboratory of
>> Computational Modeling of Biological Processes,
>> Institute of Molecular Biology, NAS RA
>> 7 Hasratyan St, Yerevan, Armenia
>> Tel: +374 93 323990
>> E-mail: h_sahakyan.mb.sci.am (h_sahakyan.mb.sci.am)
>> _______________________________________________
>> 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
> 
> _______________________________________________
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