A few thoughts
The net binding energy is essentially zero.i would not consider the sign
for such a small number. Perhaps this us a reasonable answer for this
ligand and pose.
Implicit solvent can be challenging for membrane bound systems. Read the
literature for similar work and see what they say about expected accuracy,
especially when the results were validated against experiments.
Concerning gb vs pb, on my opinion gb is a poor choice for such
calculations. It is highly approximate, often not trained for ligand
chemical species, and is most useful when speed is crucial. This is the
case for MD, but not for postprocessing.
On Sun, Sep 8, 2024, 1:27 PM Maciej Spiegel via AMBER <amber.ambermd.org>
wrote:
> Dear Amber Users,
>
> I am currently working on a protein anchored in a membrane bilayer. After
> equilibrating the system for 100 ns, I docked the potential ligand using
> AutoDock Vina and ran another 100 ns of simulations. The ligand
> consistently occupied the binding site. Subsequently, I performed MM-GBSA
> calculations and obtained a small but positive value for the interaction
> energy:
>
> -------------------------------------------------------------------------------
>
> -------------------------------------------------------------------------------
> Differences (Complex - Receptor - Ligand):
> Energy Component Average Std. Dev. Std. Err. of
> Mean
>
> -------------------------------------------------------------------------------
> VDWAALS -11.9224 2.2582
> 0.0226
> EEL -60.8192 15.3864
> 0.1539
> EGB 75.4142 12.6881
> 0.1269
> ESURF -2.6166 0.1865
> 0.0019
>
> DELTA G gas -72.7415 14.6457
> 0.1465
> DELTA G solv 72.7976 12.6124
> 0.1261
>
> DELTA TOTAL 0.0561 3.1697
> 0.0317
>
> -------------------------------------------------------------------------------
>
> -------------------------------------------------------------------------------
>
> For your reference, the input used is as follows:
>
>
> -------------------------------------------------------------------------------
> &general
> strip_mask = :WAT:K+:Cl-:PA:PE:OL:PC",
> /
> &gb
> saltcon=0.150,
> /
>
> -------------------------------------------------------------------------------
>
> I generated topologies using the command:
>
>
> -------------------------------------------------------------------------------
> ante-MMPBSA.py -p MD.prmtop -c COMPLEX.prmtop -r RECEPTOR.prmtop -l
> LIGAND.prmtop -s :WAT:K+:Cl-:PA:PE:OL:PC -n :FST
>
> -------------------------------------------------------------------------------
>
> Given the small positive interaction energy, I am wondering what could be
> the reason for this result. How should I interpret this value in the
> context of the expected binding affinity toward the pocket where the ligand
> was docked? Would doing MM-PBSA be a „solution” for the issue?
>
> Thank you for your insights.
> –
> Maciej Spiegel, MPharm PhD
> assistant professor
> .GitHub <https://farmaceut.github.io/>
>
> Department of Organic Chemistry and Pharmaceutical Technology,
> Faculty of Pharmacy, Wroclaw Medical University
> Borowska 211A, 50-556 Wroclaw, Poland
> <https://www.google.com/maps/search/Borowska+211A,+50-556+Wroclaw,+Poland?entry=gmail&source=g>
>
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Received on Sun Sep 08 2024 - 11:00:02 PDT
