Subject: partial atomic charges for autodock3

From: Matthew Lee <[email-masked]>
Date: Fri, 26 Jul 2002 16:21:26 -0700

The Autodock documentation recommends calculating the ligand charges
using AMPAC or MOPAC, but to only include *polar* hydrogens.  Isn't it
incorrect to run QM calculations on molecules that have incomplete
valencies, i.e. a carbon without its hydrogen(s)?  If one were to add all
the hydrogens to a small molecule and do either a single point calculation
or a geometry optimization for the partial atomic charges, and then remove
the non-polar hydrogens, the molecule would then be far too negative.  

	How are people using AMPAC/MOPAC in conjunction with Autodock?  Are
you leaving all the non-polar hydrogens there, and designating an additional
'h' atom type to be included for the non-polar hydrogens in the .gpf? Or is
everyone using the rule-based Gasteiger-Marsili charges?

	Also, I am wondering about the hydrogens on the macromolecule.  From
the documentation, it seems that all hydrogrens, even the non-polar ones,
present in a protein's .pdbqs file will be considered H-bond donors (as long
as the atom name starts with H).  I deduce this from 1) the statement that
"When modeling hydrogen bonds explicitly, it is necessary to add polar
hydrogens to the macromolecule.", which implies to only add polar hydrogens
to the protein and 2) the fact that the .gpf file seems to only allow for C,
N, O, S, H, X & M atom types in the macromolecule, without a separate type
'h' for non-polar hydrogens.  It seems that the available atom types for the
macromolecule are frozen, in contrast to those for the ligands, which can be
anything the user wants and can be as many as the user wants.
Interestingly, the documentation says under the DPF section of the Appendix:

------------------------
types <string>
Atom names for all atom types present in ligand.  Each must be a single
character, and only one of: C, N, O, S, H, X, or M.
------------------------
This seems erroneous, as I tried using an alternate atom name like P, or
even more vaguely like J, and autodock3 has no problem as long as 1) an
affinity map was created for that atom name by autogrid3, 2) the atom name
appears in the "types" line of the .dpf, and 3) the ATOM_MAPS in
"autocomm.h" is sufficiently large.

	In the AMBER all atom force field, hydrogen bonds are treated
implicitly by the electrostatics, with no explicit 12 10 LJ parameters.  Are
there any thoughts in the community on doing the following for setting up
the macromolecule:
1)including all hydrogens in the macromolecule 
2)using the AMBER partial atomic charges for all protein atoms
3)turning off all H-bond acceptors in the ligand by switching the ligand's
explicit H-bond paramaters for "O-H" and "S-H " in the .gpf from "12 10" to
"12 6".

	Much thanks in advance for any feedback.

--Matt Lee

*******************************************************************
Matthew Randolph Lee, Ph.D.

Computational Scientist		phone:  (858)410-6534
Lion Bioscience Inc.		fax:    (858)410-6665
9880 Campus Point Drive	      e-mail:  [email-masked]
San Diego, CA  92121
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