Jason many thanks for this. Answers my questions.
Going through the output files and the Amber11 manual, I noticed that I had NOT set PBradii to mbondi2.
How critical is this?
Can I prepare de novo my prmtop files setting PBradii to mbondi2 and then re-run MMPBSA.py using the new topology files on the trajectories generated from the topology files without mbondi2 set?
All the best
George
On Jan 4, 2011, at 10:32 PM, Jason Swails wrote:
> Hi George,
>
> These are two different GB models. While both follow the OBC equation (see
> the Onufriev, Bashford, Case paper describing them, cited in the Amber
> manual), the alpha, beta, and gamma parameters are different between the two
> of them, so you can't expect the results to be the same.
>
> Try using the same GB model and you should get the same results.
>
> Good luck!
> Jason
>
> On Tue, Jan 4, 2011 at 12:35 PM, George Tzotzos <gtzotzos.me.com> wrote:
>
>> Hi Jason,
>>
>> Many thanks for the comprehensive replies.
>>
>> With regard to your question if the difference is between the serial and
>> parallel implementations of MMPBSA.py the answer is NO. Both runs were made
>> with the parallel implementation.
>>
>> The only difference is that in the per-residue decomposition igb was set to
>> 5 (default) whereas in the calculation of total energy igb was set to 2.
>>
>> Please see the namelists below.
>>
>> George
>> ==========================
>>
>> Per-residue GB and PB decomposition
>> &general
>> endframe=50, verbose=1,
>> /
>> &gb
>> igb=5, saltcon=0.100,
>> /
>> &pb
>> istrng=0.100,
>> /
>> &decomp
>> idecomp=1,
>> dec_verbose=1,
>> /
>> ===========================
>>
>> Input file for running PB and GB
>> &general
>> endframe=50, verbose=1,
>> # entropy=1,
>> /
>> &gb
>> igb=2, saltcon=0.100
>> /
>> &pb
>> istrng=0.100,
>> /
>> ============================
>> On Jan 4, 2011, at 7:59 PM, Jason Swails wrote:
>>
>>> Hello,
>>>
>>> My comments are below.
>>>
>>> On Tue, Jan 4, 2011 at 3:41 AM, George Tzotzos <gtzotzos.me.com> wrote:
>>>
>>>> Happy New Year to all,
>>>>
>>>> I've been running MMPBSA.py.MPI to determine Delta G for a
>> protein-ligand.
>>>> I've also run the program to determine per residue decomposition of
>>>> entropy.
>>>>
>>>
>>>> The same input files have been used in both cases. The the Delta G
>> results
>>>> obtained from Generalized Born differ by ~ 2kcal/mol
>>>>
>>>
>>> Is this the difference between parallel and serial or the difference
>> between
>>> decomp turned on and decomp turned off? Also, what individual terms
>> differ
>>> between the two calculations? It could be that the algorithm used to
>>> compute the surface area between the two methods is slightly different.
>>>
>>>
>>>>
>>>> For example,
>>>>
>>>> Differences (Complex - Receptor - Ligand):
>>>>
>>>> DELTA G binding = -46.6213 +/- 3.1112
>>>> 0.1663 (given by per-residue entropy
>>>> decomposition)
>>>> DELTA G binding = -44.2279 +/- 2.7619
>>>> 0.1476 (without per-residue entropy
>>>> decomposition)
>>>>
>>>> The same discrepancy of ~2kcal/mol has been observed using the same
>> ligand
>>>> with two (2) other receptors.
>>>>
>>>> The Poisson Boltzmann calculations with and without per residue
>>>> decomposition gave identical values
>>>>
>>>
>>> As far as I know, the surface area is non-decomposable for PBSA, so this
>> is
>>> not really a factor. Hence, you get similar/identical results.
>>>
>>>
>>>>
>>>> Differences (Complex - Receptor - Ligand):
>>>>
>>>> DELTA G binding = -34.0898 +/- 3.1112
>>>> 0.1663
>>>>
>>>> My specific questions are the following:
>>>>
>>>> 1. Is there an explanation for this discrepancy in the case of
>> Generalized
>>>> Born while this discrepancy is not observed in the Poisson Boltzmann
>>>> calculations?
>>>>
>>>> 2. The Delta Gs given by the two methods are different by ~10 kcal/mol.
>>>> That strikes me as being too much of a difference.
>>>>
>>>
>>> This is not unusual, and reflects the method's shortcomings when
>> calculating
>>> absolute binding free energies. A better comparison to make would be the
>>> DELTA Delta G between different receptors with the same ligand or
>> different
>>> ligands with the same receptor.
>>>
>>>
>>>>
>>>> 3. Is temperature (say 300K) factored in the ENTROPY calculations?
>>>>
>>>
>>> Yes. There should be a comment in the output file saying exactly that.
>> On
>>> the tutorial website, the last line of text in the output file says
>>>
>>> NOTE: All entropy results have units kcal/mol. (Temperature has already
>> been
>>> multiplied in as 300. K)
>>>
>>>
>>>> 4. Can one assume that the enthalpy for the six translational and
>>>> rotational degrees of freedom is 6*(1/2)*RT=1.8 kcal/mol at 300K?
>>>>
>>>
>>> No. The entropy is calculated from statistical mechanical equations
>> using
>>> the partition function assuming that the translational, rotational, and
>>> vibrational parts of the Hamiltonian are separable. This introduces a
>>> mass-dependence of the translational entropy.
>>>
>>> Note that this email was begun in response to your first message, so my
>>> later email will address future questions.
>>>
>>> Good luck!
>>> Jason
>>>
>>>
>>>> Thanks in advance and best regards
>>>>
>>>> George
>>>>
>>>> _______________________________________________
>>>> AMBER mailing list
>>>> AMBER.ambermd.org
>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>
>>>
>>>
>>>
>>> --
>>> Jason M. Swails
>>> Quantum Theory Project,
>>> University of Florida
>>> Ph.D. Graduate Student
>>> 352-392-4032
>>> _______________________________________________
>>> 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
>>
>
>
>
> --
> Jason M. Swails
> Quantum Theory Project,
> University of Florida
> Ph.D. Graduate Student
> 352-392-4032
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
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Received on Wed Jan 05 2011 - 04:30:03 PST
