ADL: Best way to assign partial charges
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  and
AMBER force field  equations: ΔGvdW, ΔGH-bond and ΔGelec are similar
up to a weight (W) factor.
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)
> 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 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
More information about the autodock