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
into yourself.
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.
Mark
--
gmx-users mailing list [email protected]
http://lists.gromacs.org/mailman/listinfo/gmx-users
* Please search the archive at
http://www.gromacs.org/Support/Mailing_Lists/Search before posting!
* Please don't post (un)subscribe requests to the list. Use the
www interface or send it to [email protected].
* Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
