[gmx-users] Discrepancy between Free Energy Perturbation using Gromos96 and OPLS

Sandeep Somani ssomani at bii.a-star.edu.sg
Wed Oct 12 06:01:54 CEST 2005 

Hi All 

I have a clue on the origin of this discrepancy. Looks like a bug in FEP
code. 
Would like to get comments from the developers. 

The system I am working with is a 153 residue protein with a buried
(isolated from solvent) water molecule. I am trying to find the free
energy of binding of this buried water by perturbing the non-bonded
interaction of the *single water molecule*. 

The deltaG values using different ff and gmx3.3beta are

1. OPLS ff for protein    :  ~ -330 kJ/mol         
2. Gromos96 (ffG43a1.itp) :  ~  -37 kJ/mol    

Clearly OPLS is incorrect. 

Using -sepdgdl option of mdrun in gmx3.3beta to get the components of
dG/dl, 
a sample entry in the log file at lambda=0.5 looks like  

GROMOS
======
Step 1000: non-bonded V and dVdl for node 0:
  VdW and Coulomb SR particle-p. V -3.34460e+05  dVdl  8.61080e+01
  RF exclusion correction        V -1.01159e+04  dVdl  5.09968e-02
Step 1000: bonded V and dVdl for node 0:
  G96Angle                #2306  V  2.50156e+03  dVdl  0.00000e+00
  Proper Dih.             # 857  V  1.30637e+03  dVdl  0.00000e+00
  Improper Dih.           # 743  V  7.88975e+02  dVdl  0.00000e+00
  LJ-14 + Coulomb-14      #2561                  dVdl  0.00000e+00
------
OPLS
====
Step 1000: non-bonded V and dVdl for node 0:
  VdW and Coulomb SR particle-p. V -3.42520e+05  dVdl  1.15979e+02
  RF exclusion correction        V -1.55339e+04  dVdl  7.03910e-02
Step 1000: bonded V and dVdl for node 0:
  Angle                   #4465  V  4.88804e+03  dVdl  0.00000e+00
  Proper Dih.             # 467  V  2.79401e+02  dVdl  0.00000e+00
  Ryckaert-Bell.          #5037  V  1.80946e+03  dVdl *-3.39702e+02*
  LJ-14 + Coulomb-14      #6445                  dVdl  0.00000e+00
--------

The numbers are reasonable for Gromos. 
But in OPLS there is a big and non-zero "Ryckaert-Bell." term even
though there are no dihedrals 
in the perturbed atoms. Whats the origin of this ? And how can i get rid
of it ?  
Relevent portions of the OPLS topology file are attached. 

also, in the log file what do the numbers starting with # mean (#4465, #
467 etc) ? 

With Regards
Sandeep 

---
Research Associate
Computational Biology Group
Bioinformatics Institute
Singapore

http://www.bii.a-star.edu.sg/~ssomani






> -----Original Message-----
> From: gmx-users-bounces at gromacs.org 
> [mailto:gmx-users-bounces at gromacs.org] On Behalf Of Sandeep Somani
> Sent: Tuesday, October 04, 2005 5:57 PM
> To: 'Discussion list for GROMACS users'
> Subject: RE: [gmx-users] Discrepancy between Free Energy 
> PerturbationusingGromos96 and OPLS
> 
> 
> Adding to that, as per David's suggestion, I installed 
> gmx3.3_rc3 and ran the same simulation again. 
> 
> The values are still similar i.e. ~ -30kJ/mol for Gromos96 
> and < -300kJ/mol for OPLS. 
> 
> I tried again with PME too .. still the OPLS values are much 
> lower than Gromos. 
> 
> am quite clueless now ! ill be happy to provide the input 
> files if anyone wants to probe further .. 
> 
> Regards
> Sandeep 
> 
> 
> 
> 
> > -----Original Message-----
> > From: gmx-users-bounces at gromacs.org
> > [mailto:gmx-users-bounces at gromacs.org] On Behalf Of Maik Goette
> > Sent: Tuesday, October 04, 2005 5:41 PM
> > To: Discussion list for GROMACS users
> > Subject: Re: [gmx-users] Discrepancy between Free Energy 
> > Perturbation usingGromos96 and OPLS
> > 
> > 
> > Hi David
> > 
> > Could you be a bit more precise?
> > Is this difference due to a problem of united 
> atoms/reaction field or
> > all atoms/reaction field. For I also use FEP with all atoms 
> > (amber99-port) and reaction field, I could use some info. :)
> > 
> > Regards
> > 
> > Maik Goette, Dipl. Biol.
> > Max Planck Institute for Biophysical Chemistry
> > Theoretical & computational biophysics department
> > Am Fassberg 11
> > 37077 Goettingen
> > Germany
> > Tel.  : ++49 551 201 2310
> > Fax   : ++49 551 201 2302
> > Email : mgoette[at]mpi-bpc.mpg.de
> >          mgoette2[at]gwdg.de
> > WWW   : http://www.mpibpc.gwdg.de/groups/grubmueller/
> > 
> > 
> > David wrote:
> > > On Sat, 2005-10-01 at 13:11 +0800, Sandeep Somani wrote:
> > > 
> > >>hi all
> > >>
> > >>I did a Slow Growth (dummy -> real) based FEP of a small
> > ligand bound
> > >>to a protein using Gromos and OPLS ff. Description of
> > ligand in both
> > >>cases is identical.
> > >>
> > >>Free energy change from the Gromos simulation is 
> reasonable but the
> > >>number from OPLS is an order of magnitude more negative.
> > >>
> > >>All parameters (reaction field electrostatics, constraints in
> > >>topology, delta-lambda etc) other than the ff are 
> > identical. Am using
> > >>gmx3.2.1.
> > >>
> > >>Has anyone encountered this before ? what could be the
> > origin of this
> > >>discrepancy ?
> > > 
> > > It could be due to the all-atom/united atom difference in
> > combination
> > > with the reaction field. Berk has recently implemented an 
> exclusion
> > > correction for reaction fields that could be important 
> > here. You could
> > > retry it with 3.3beta to see whether there is a difference.
> > > 
> > > 
> > > 
> > >>Thanks and Regards
> > >>Sandeep
> > >>
> > >>---
> > >>Research Associate
> > >>Computational Biology Group
> > >>Bioinformatics Institute
> > >>Singapore
> > >>
> > >>http://web.bii.a-star.edu.sg/~ssomani/
> > >>
> > >>
> > >>
> > >>
> > >>
> > >>
> > >>
> > >>
> > >>_______________________________________________
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