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
>>
>> _______________________________________________
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>> http://lists.ambermd.org/mailman/listinfo/amber
>>
>
>
>
> --
> Jason M. Swails
> Quantum Theory Project,
> University of Florida
> Ph.D. Graduate Student
> 352-392-4032
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Received on Tue Jan 04 2011 - 12:00:04 PST
