Are the simulations for MM/PBSA done in explicit solvent, and those for
MM/GBSA done in implicit solvent? This should be the case, that is, you
shouldn't use the same simulation to do both. Also keep in mind that for
your MM/?BSA input file, the surface tension term will potentially be
different. For MM/PBSA the default is something like 0.072, whereas if you
do GBSA simulations, and turn on gbsa (gbsa=1 in the config file) the
default is 0.005. Moreover, if you didn't explicitly turn on gbsa, it is
off by default, and so the actual surface tension term you should use for
your MM/GBSA calculations is 0.
~Aron
On Wed, Feb 27, 2013 at 7:28 PM, Vivek Shankar Bharadwaj <
vbharadw.mymail.mines.edu> wrote:
> Hi AMBER Users,
>
> I am new to MMPB/GBSA calculations and am studying the binding of toluene,
> fumaric Acid and benzylsuccinate to an enzyme. I was able to get the
> implementation to work successfully for my system. I have some questions
> regarding the analysis.
>
> I have been able to calculate the overall binding energies using MMGBSA,
> MMPBSA and decompose the binding energies among the key residues at the
> active site.
>
> I have the following questions with regards to analyzing the results
>
> 1. I find that the total binding free energies calculated from MMGBSA give
> negative free energies of binding while the MMPBSA binding energies are
> positive (~1 kcal/mol). Why would the MMPBSA free energies show
> unfavourable binding while MMGBSA show favourable? The MMGBSA and MMPBSA
> energies also do not display the same trend for my ligands.
>
> 2. I understand that the ligand also has to be mentioned in the print_res
> specification for decomposition. In the output, (delta's total energy
> section) the ligand contribution to the binding energy is also reported. I
> am finding it difficult to understand how the ligand's binding energy be
> decomposed onto itself?
>
> 3. I find that the majority (~90%) of the binding energy (deltas of the
> total energies in the output) for the toluene binding is attributed to the
> ligand itself. [Meaning that the B.E remains undecomposed]. What could I be
> doing wrong? or is this due to the hydrophobic interactions stabilizing
> toluene? In the case of fumaric acid the ligand contribution was ~20% only.
>
> These were calculated from 20ns trajectories of the substrate bound
> simulations with the substrate stable at the active site.
>
> I will be grateful to any comments/guidance on how I can better understand
> or improve my results.
>
> Thank you.
>
> --
> Vivek S. Bharadwaj
> Graduate Student
> Department of Chemical and Biological Engg.
> Colorado School of Mines
> Golden Colorado
> _______________________________________________
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> http://lists.ambermd.org/mailman/listinfo/amber
>
--
Aron Broom M.Sc
PhD Student
Department of Chemistry
University of Waterloo
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Received on Wed Feb 27 2013 - 17:00:03 PST
