Hi Maryam,
If you're keen to share the complex parameter and 10 frames from your MD
with stripped solvent I can have a quick look to see if I can spot any
errors.
Cheers,
Bruno
On 04/10/16 09:17, David A Case wrote:
> 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
>
>
> _______________________________________________
> 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
Received on Tue Oct 04 2016 - 07:00:03 PDT
