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

Erik Lindahl lindahl at sbc.su.se
Wed Oct 12 11:21:53 CEST 2005 

Hi Sandeep,

This could indeed be a bug. Please enter a report at http:// 
bugzilla.gromacs.org and include the appropriate files to reproduce  
it as attachments.

We'll probably have a look at it anyway, but it's going to be longer  
if we need to construct a system to reproduce it first :-)

Cheers,

Erik

On Oct 12, 2005, at 6:01 AM, Sandeep Somani wrote:

> 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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-----------------------------------------------------------
Erik Lindahl  <lindahl at sbc.su.se>
Assistant Professor, Stockholm Bioinformatics Center
Stockholm University, SE 106 91 Stockholm
Phone: +46 8 5537 8564     Fax: +46 8 5537 8214

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