Subject: Some questions about Dock 4.0

From: Maneesh Yadav <[email-masked]>
Date: Wed, 09 Jun 1999 15:57:44 -0700

Hello all, I am new to the list, so if this discussion has recently come
up, a pointer would be appreciated.  I am comparatively new to this
field, so the questions I have may be classified as beginner status, but
please bear with me.

We are doing some experiments of substrate binding to internal protein
cavities, and for a screening of possible substrates we are using Dock
4.0.  I have go the program working for single ligand binding (and has
given me some fair results) but I do have some questions, any advice on
the following would be appreciated.

A) Multiple Ligands

I have saved an FDAT file from the CSD, and converted to PDB format (via
fdat2pdb).  Now, when I convert to mol2 via pdb2syb, I get messages
like:

 pdb2syb binder.pdb
  H4  in . for C-            2
  NI1 in . for C-            2
  O5  in . for C-            2
  O6  in . for C-            2
  O7  in . for C-            2
            5  isolated atom(s) omitted from . for C-
Error--no bond length information for atom  A in . for C-
 Skipping . for C-
  C3  in . for C-            3
  C4  in . for C-            3
  C5  in . for C-            3
            3  isolated atom(s) omitted from . for C-

I am assuming this is due to the fact that the respective crystal
structures are somehow incomplete?
And then when I try to pass these to Dock, it gives errors like,

WARNG read_mol2: Improper ATOM record substructure id for _ . for C- in
binder
.mol2

and no real output.  Is this something unpreventable or have their been
some changes in the database format of CSD?

Another thing is that I am currently querying the CSD for structures
that have between 1-25 C atoms, what I really want is to get a large
number and variety of small molecules that could fit in a sphere of
radius ~4.5A (about the cavity radius).  Does anyone have a better
method of a volume constraint based query (even for another database)?

B) Chemical Screening/Matching

When I insert the color table into the the .sph file at the appropriate
place,

color hydrophobic 1

(each sphere in my cluster is labeled hydrophobic)

and then label the last (color) column correspondingly 1; I turn
chemical matching on and Dock says that the "label hydrophobic is
undefined" and doesn't read the file
BTW I am pointing Dock to the right definition tables.

Chemical scoring at least reads the file, but I am suspicious of the
results as a hydrophobic molecule generated a positive chemical score
and a charged molecule has given me a sizable negative score!  Am I
doing something obviously wrong?

I have also tried directing my questions to members of the Kuntz group,
but they seem rather busy right now and have been unable to respond.

Many Thanks in Advance,

Maneesh Yadav
[email-masked]