[gmx-users] Ligand Internal energy
Mark.Abraham at anu.edu.au
Thu Sep 6 04:43:08 CEST 2012
On 6/09/2012 12:08 PM, Tom Dupree wrote:
> I am trying to differentiate between several binding poses for a protein
> ligand complex.
Then you need to measure the free energy differences between them. No
single configuration is ever going to tell the whole story, and maybe
not even a part of it. One option might be to use thermodynamic
integration to annihilate the ligands, so that you have a path between
the states, but there's a big literature there that you'll need to look
> Initially I tried the LIE method however its results do not followed the
> expected trend based on experimental data. I then looked at the raw
> interaction energies between the ligand and its environment (LIG-rest in
> g_energy). This gives better relationship but still fails to explain the
> experimental results. I now want to select some representative frames for
> analysis with external scoring functions.
Inasmuch as they may approximate the above, that's a good thought. But
rather than try to guess what the "best" conformations are, run a
simulation of the bound ligand, cluster the protein-ligand conformations
(to approximate the free energy surface of the bound ligands), compute
things based on the cluster centers, and reweight by the cluster
populations. This is a crude approximation to the above.
> I would like to select the frames that have the strongest interactions and
> least ligand strain. How do I obtain the internal energies for the ligand
> alone? (bending, twisting, stretching etc?)
That ignores the strain of the protein... However, trjconv and tpbconv
will allow you to carve matching subsets of your trajectory and .tpr for
use with mdrun -rerun.
> Also should I include the
> LIG-LIG LJ and Coul energies?
Shrug, might as well add some more random numbers :-) Force fields were
not parametrized to be additive in this way, so it's not a surprise that
they mostly don't work in this way.
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