ADL: Best way to assign partial charges

Sargis Dallakyan sargis at scripps.edu
Thu Apr 16 11:33:35 PDT 2009


Douglas Houston wrote:
> I've tried to find out as much as I can about the best way to assign partial charges to the receptor, but I've only succeeded in making myself more confused.
> 
> According to the manual, "appropriate partial atomic charges must be assigned. This can be achieved by
> the user’s preferred method, e.g. using InsightII, Quanta, Sybyl, AMBER or CHARMm. Alter-
> natively, one of the shell scripts described in the Appendix can be used."
> 
> According to the FAQ on the website, "the AD4 scoring function was calibrated using Gasteiger partial charges on both the ligand and the macromolecule."
> 
> But according to the front page of the website "AutoDock 4.0 now has a free-energy scoring function that is based on ... the AMBER force field"
> 
> So can anyone answer the following questions:

> 1. Does the scoring function use Gasteiger charges or the AMBER force field?

It is my understanding that AutoDock 4.0 is using Gasteiger charges and 
the AMBER force field. If you look at the AutoDock force field [1] and 
AMBER force field [2] equations: ΔGvdW, ΔGH-bond and ΔGelec are similar 
up to a weight (W) factor.

[1] http://autodock.scripps.edu/resources/science/equations/
[2] http://ambermd.org/eqn.txt

As you probably know, previous version of AutoDock (3.0) was calibrated 
using Kollman charges for protein, which I believe is the same as AMBER 
charges. From the computational point of view Kollman/AMBER charges are 
taken from a lookup table whereas Gasteiger-Marsili charges are computed 
  using Partial Equalization of Orbital Electronegativities (PEOE) 
algorithm.

> 2. Was AD4 calibrated using Gasteiger charges assigned by the prepare_receptor4.py script? If not, how exactly were they assigned?

I think so.

> 3, Is there an "official" recommended way of assigning charges to the receptor before calculating grids, and if so, what is it?

I've recently done virtual screenings with PyRx 
(http://mgldev.scripps.edu/PyRx), where I used Gasteiger charges 
computed by PyBable module which is a re-implementation of Babel 1.6 in 
Python and which is used by prepare_receptor4.py and prepare_ligand4.py. 
I then computed Gasteiger-Marsili partial charges using openbabel 2.2.0 
(http://openbabel.org/wiki/Gasteiger-Marsili) and used that charges in 
pdbqt files for the ligands. There are noticeable changes in the 
numerical values between these two methods, however, the final top 10 
ranked compounds were almost identical.

The bottom line is that it is "official" recommended to use 
prepare_receptor4.py and prepare_ligand4.py to assign partial atomic 
charges, however users are free to chose any other packages they want.

Hope this clarifies things a bit.

Sargis


-- 

Sargis Dallakyan, Ph.D. - Research Programmer III
The Scripps Research Institute,
Dept. Molecular Biology,  MB-5,
10550  North Torrey Pines Road,
La Jolla,  CA 92037-1000
Tel: (858) 784-9559
http://mgltools.scripps.edu/Members/sargis



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