On Tue, Oct 04, 2016, Maryam Hamzehee wrote:
> However, by using the MM-PBSA
> calculation (tutorial A3), the result was surprising. The binding
> free energy for the complex of small ligand -receptor was around
> ~-4000kCal/mol based on GB calculations. Should I use ante-MMPBSA.py for
> generating of the ligand, receptor, and complex from the solvated form
> of complex?
(I usually try to avoid repeating previous advice, but will break that rule
here: the following is aimed at everyone on the list, not just at this
problem.)
Free energy calculations are an advanced subject, and require diligence
and experience to carry out correctly. Scripts like MMPBSA.py or
ante-MMPBSA.py are useful tools for experienced users to automate the
calcualtions, but they are complex, and cannot possibly trap all errors.
Running MM/GB-SA calculations "by hand" (without the use of any of these
scripts) is not all that difficult: set up three GB trajectories (ligand,
receptor and complex); collect the average energies (in various categories,
e.g. bonds, angles, etc.) from each the three simulations; do the appropriate
subtractions. Use VMD or Chimera to visualize each of the trajectories to
make sure that they are doing reasonable things.
Once you do this, you should have a set of sample results that you fully
understand. If you get nonsensical binding energies, see if you can narrow
down the problem. By all means, post here if you get stuck. If you get
reasonable results that you understand, then you can re-try the automated
scripts--you will have a much better chance of finding out what is going
wrong.
It is certainly possible (even likely) that using ante-MMPBSA.py
will fix the problems you have encountered. If that happens, you can set
aside the "by hand" sample calculations that you did. But I strongly
recommend avoiding the automated scripts at the very beginning--after all,
I wrote the paragraphs at the beginning of Chap. 31 that make the same
point.
...good luck....dac
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Received on Tue Oct 04 2016 - 05:30:03 PDT
