Subject: Re: CCL:explicit connectivity for PDB structure in Gaussian

From: Eric Bennett <ericb[at]pobox.com>
Date: Tue, 14 Dec 2004 11:06:35 -0600

Lily wrote:

>I read a PDB structure into Gaussian and found that the bond order for
>binding ligand is not right. I guess it is because the initial structure
>is not good enough for proximity criteria in Gaussian. Then I wonder how
>to make sure the bond order for both enzyme and substrate is right and
>since it is a big system, it is hard to check manually. 
>I really appreciate if you could let me how to get the right
>connectivity either changing parameter set up or using other package.
>(Prefer free available) 
>
>Thanks a lot,
>
>Lily
>
It appears that OpenBabel (free) will correctly assign bond orders to 
protein residues if you use it to convert your PDB file to mol2 format 
(which stores bond order information in the .mol2 file):
babel -ipdb file.pdb -omol2 file.mol2
http://openbabel.sourceforge.net/

I don't use Gaussian but I presume it's smart enough to use the bond 
order information stored in a mol2 file.

Commercial packages like Insight and Maestro can also assign protein 
bond orders, if you have access to either of those and don't feel like 
compiling OpenBabel... Maestro is nice because if it doesn't recognize a 
particular molecular fragment, it colors it differently from the rest of 
the molecule so you know to check the bond orders.

But unless you are screening a large library of structures, it's best to 
always check your ligands manually, no matter how large they are and 
even if you are using a program which usually gets the bond orders 
right.  You might be surprised at the number of ligands in the PDB that, 
upon close inspection (sometimes it doesn't even require close 
inspection!), appear to have been refined incorrectly because (a) they 
have obvious distortions from the expected geometry, (b) the x-ray 
resolution is low enough that such deviations should be assumed to be 
errors unless otherwise explained and (c) the authors don't bother to 
comment on the origin of the deviations in their paper.

You'll probably want to manually inspect certain types of residues 
anyway, to make sure the protonation states make sense given available 
hydrogen bonding partners, and to correct for slip-ups like glutamines 
and asparagines that need to have their side chain ends flipped to make 
sensible h-bonds.  Some commercial packages automate this task, but I 
would still check the active site area to make sure the results are 
sensible. 

-- 
Eric Bennett, Center for Drug Design, U of Minnesota