ADL: Problem with docking results for Lipoxygenase with Protocatechuic Acid.

Sim Kar Seng karseng76 at yahoo.com.sg
Wed Jan 2 08:50:58 PST 2008


Dear all,
 
I'm a new Autodock user and is starting on some docking test.I have some
questions regarding the results of my docking and will like to seek some
advices.
 
I've taken the Lipoxygenase with protocatechuic acid complex (PDB: 1n8q) for
a docking test and have tried docking with different grid size and search
parameter. I've removed all the water molecule and the ligand for the
macromolecule and use PRODRG to obtain the structure for the protocatechuic
acid (DHB) ligand. 
 
In the original structure, the ligand (DHB) was found to have a hydrogen
bond to the HIS523 residue. This was found by using the Build command in the
Hydrogen Bonds menu in ADT. One question here is whether this is the correct
method to find out where the ligand is bonding to?
 
In a few preliminary dockings where I have a larger grid size (as large as
126x126x126), none of the docked pose were near to the ligand position in
the original complex even with higher search parameters like max number of
evaluations of 25000000, max number of generations of 100000 and ga_run of
12. In each case, the results have poor clustering and the ligand were away
from the original location in the complex. However, the best docked energy
in some of these clusters are around -7.XX.
 
Subsequently, I've try to restrict the grid map size down to 60x60x60 and
centered around the the HIS523 residue that the ligand binds to in the
original complex and perform a docking with the higher search parameters as
above but with a ga_run of 20. The results did converge to a good clustering
and docked pose were quite near to the HIS523 residue that the ligand docked
to in the original complex. However, the docked energy for all pose were
quite near at around -5.XX. In addition when I use the build command in the
Hydrogen Bonds menu in ADT to build the bond, the bonds were not to the
HIS523 residue as in the original complex.
 
There's a few question to the above observation. 
- Is it abnormal/uncommon to find a lower docked energy when performing the
docking with a smaller grid and with higher search parameters settings? 
 
- In this case, the docking with a good clustering is the one closer to that
in the original complex but have a lower docked energy. So in general,
should I place more emphasis on getting a good cluster than a lower docked
energy?
 
- Should I be concern that in the above final docking with the best
clustering, the hydrogen bond does not match with that in the original
complex? As a whole, given the above, can I consider the above to be an
accurate/successful docking or does it mean that the ligand fails to dock
correctly?
 
My most sincere apologies for the very long posting as I'm not sure how to
put it across without missing too much details. Thank you for your patience
and any advice will greatly be appreciated. 
 
Brgds,
Kar Seng
 


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