Subject: 2D to 3D strux conv: summary

From: Scott William Chinn <[email-masked]>
Date: Tue, 25 Jul 95 10:04:39 PDT

Greetings to all!

Thank you for all of your responses! The information was most 
helpful.

Here is a summary:
First is the question that I asked and following is the 
responses.

> Date: Wed, 19 Jul 95 02:18:47 PDT
> From: Scott William Chinn <[email-masked]>
> Subject: CCL:2D to 3D structure conversion
> 
> I understand that programs such as CONCORD, CORINA and 
CHEM-X
> can convert 2D structures to 3D. 
> 
> I have a number of 2D structures which I would like to 
> convert to 3D and then store in a relational database.
> 
> Is this possible? What does the 3D data look like? I have 
heard
> that CHEM-X will give you something like 400 bitwise 
operators, > which somehow describe the 3D stucture. Is this 
correct?

Conversion from 2D to 3D is a function offered by several 
packages
(including ours).  Basically, a set of relatively simple rules 
is used
to generate 3D geometry, using standard bond lengths and 
angles.  The big
problem is that the 2D structure is usually quite different 
>from the
desired 3D result; often the 2D structure doesn't have a lot 
of cues for
stereochemistry or overall conformation.  You should check the 
results
of such an automated conversion before using them.  (After 
all, even in
doing a 3D structural optimization by standard methods one 
sometimes
finds a local minimum that is, by the standards of an 
intelligent chemist,
obviously a poor structure.  A 2D --> 3D structure conversion 
is a still
cruder operation.)

I don't know relational databases.  When HyperChem does a 2D 
--> 3D
conversion, what comes out is a 3D structure: each atom has 3D 
coordinates
and a set of bonds to other atoms.

Regards,
Joel
 
------------
Joel Polowin, Ph.D.   Manager, Scientific Support
Email to: [email-masked] 

Scott,

It is certainly possible.  I have some experience with 
CONCORD, having used
it to convert isomeric SMILES strings to pdb files (there are 
more choices
of input and output formats).  The pdb files produced contain 
the smiles
string, the Cartesian coordinates, and a connection table, and 
can easily
be read by humans or other programs.  You can view several 
hundred at
http://ibc.wustl.edu/klotho/.  If your SMILES string doesn't 
specify the
stereochemistry, CONCORD will try and choose for you.  The 
structures it
gets usually accord pretty well with both chemical intuition 
and crystal
structure (see J. Chem. Info CS 33:155-163, 1993), though it 
does have
limitations and does sometimes produce a howler.  I have no 
experience with
Corina yet, but from what I hear and read its strengths are 
complementary
to CONCORD's weaknesses and would be a good alternative 
(please let's not
have a flame war).  They now have a free email server, and I'm 
planning to
try it out (it's been reported on this list just recently).  I 
have no
experience with ChemX.  The hardest part may be generating the 
input for
the conversion program; if you think Klotho would be of some 
assistance to
you please let me know.

You may be able to find coordinates for your molecules.  For 
example the
NCI has its files up on a gopher server, though last time I 
looked there
was no easy way of retrieving a specific molecule.  Try the 
NIH web site, I
think there is a pointer from there (sorry I am unable just 
now to give you
the complete address).  Data from Cambridge Crystallographic 
Database are
proprietary.  I know a number of software vendors sell 
databases of small
molecules in various forms, usually bundled with their 
software.

You may want to give some thought to the types of queries you 
wish to run:
this has a significant impact on choice of database model, 
organization of
the database, and representation of the data.

Good luck,

Toni Kazic
Institute for Biomedical Computing
Washington University

Scott,

> I understand that programs such as CONCORD, CORINA and 
CHEM-X
> can convert 2D structures to 3D. 

I have used all three of the programs mentioned to convert 
tens of thousands of
structures.  They all have their strengths and weaknesses. 
Chem-X is a database
and modeling program that has a 2D-3D converter as one module. 
The converter is 
really there for people who don't want to buy a separate 
conversion program. It has
some serious limitations as shipped ( mainly the inability to 
build large rings ) but 
has the advantage that the build fragment library is 
completely open to the user, so
fragments can be added or changed. Be aware that unlike the 
other programs listed
above, the Chem-X converter doesn't really attempt to find a 
good conformation, it
expects that you will go on to 3D key the structure and use 
the replace option to
replace the built structure with the best conformation found 
in the search.  If you 
don't do this step you can have some really bad structures.  
CONCORD is the oldest of 
these converters. We have routinely used CONCORD to handle 
Chem-X build failures and
find that it is successful 80-90% of the time ( excluding 
organometallics ). You
might want to look at our WWW page ( 
http://www.ncifcrf.gov:1994/DTP/dis3d.html ) for
some more detailed information on this. We have done some 
testing with CORINA and
think we will end up using it for all our conversions.

>   I have a number of 2D structures which I would like to 
> convert to 3D and then store in a relational database.

Be aware that CONCORD and CORINA have no database 
capabilities. If you want to 
store the 3D structures in an ORACLE database you may want to 
investigate the
program RS3 from PSI.  
 
> I have heard
> that CHEM-X will give you something like 400 bitwise 
operators, which
> somehow describe the 3D stucture. Is this correct?

Like most 3D search programs, Chem-X has a bit screen to do 
very fast preliminary
searches.  The bit screen is based on center to center 
distances.  The centers
that Chem-X defines are:

H-bond donor
H-bond acceptor
positive charge
aromatic center
hydrophobic center

The five center lead to 15 pairwise distance keys, each with 
31 bits representing
a certain distance range. There are also 2 keys encoding bond 
type patterns
and 1 key that encodes formula information.  The total of 18 
keys times 31 bits
gives 558 binary descriptors.  

Hope this helps.

DanZ.

/*************************************************************
*********
 *  Dan Zaharevitz
 *  Information Technology Branch, Developmental Therapeutics 
Program
 *  National Cancer Institute
 *  EPN Room 811,  6130 Executive Blvd.     Rockville, MD 
20892-9903
 *  email:  [email-masked]      phone:  
(301)496-8747
 
**************************************************************
********/
 
> I have a number of 2D structures which I would like to 
> convert to 3D and then store in a relational database.
> Is this possible? What does the 3D data look like? I have 
heard
> that CHEM-X will give you something like 400 bitwise 
operators, which
> somehow describe the 3D stucture. Is this correct?

I assume that you want to search within your database of 3D 
structures
for those compounds which satisfy certain chemical and 
3D-geometric
specifications.  Accomplishing this objective with standard 
relational
database software would be *extremely* awkward and 
inefficient.  Special
3D searching systems (databases and search engines) have been 
developed
specifically for this purpose.  Usually, in the course of 
performing
such 3D searches, it is very important to account for the 
conformational
flexibility of the compounds in the database.  

MDL, Tripos, and Chemical Design Ltd. are the three leading 
distributors
of chemical database software.  MDL and Tripos offer the most 
robust and
efficient software, particular with respect to conformational 
flexibility
within the searching process.  Tripos software is also tightly 
interfaced
with molecular modeling and analysis software which provides 
substantial
advantage while analyzing the "hits" found from a 3D search.

> I understand that programs such as CONCORD, CORINA and 
CHEM-X
> can convert 2D structures to 3D. 

All three are good converters.  The CHEM-X builder generates 
multiple
conformations which are useful only with Chemical Design 
searching
software.  In my opinion, this is not the proper approach to 
handling
the conformational flexibility issue.  CONCORD and CORINA both 
generate
a single, low-energy structure which the Tripos and MDL 
searching software
"flex" as necessary.  For a variety of reasons, CONCORD is, by 
far, the most
widely used and generally accepted 2D to 3D converter.  It is 
distributed
by Tripos.

Hi Scott,

The program, CONVERTER, from Biosym Technologies can also be 
used
to convert 2D Databases to 3D Databases.  It accepts as input
an MDL sd file of 2D structures (having the input coordinates
all zero'ed out is also acceptable) and writes out a 
corresponding
output sd file of 3D structures.  One of its interesting 
capabilities
is the ability to automatically recognize chiral centers in 
your
molecule whose chirality is not assigned (via wedge bonds or
parity flags in the SD file) and generate multiple output 
structures
corresponding to different chirality assignments to the chiral 
atoms.
A comparison of the program to some other programs appears in:
E.M. Ricketts et al, J. Chem. Inf. Comp. Sci., Vol. 33, pp. 
905-925 (1993).

Regards,

Marvin Waldman, Ph.D.
Director, Rational Drug Design
Biosym Technologies, Inc.
e-mail: [email-masked]

Dear Scott,

we used CONCORD for the 2D/3D conversion of some 200,000
structures which were available in MDL SD-file format. The
3D structures were stored in UNITY from Tripos which we
use for 3D searches. It allows to search for 3D atom patterns 
taking the conformational flexibility into account. It does a 
good 
job but UNITY is pretty expensive.
The same can be done with the MDL product ISIS-3D. Also
not cheap. It is available for VAX, RS-6000 and SGI. We use
MDL software in our company, but we have no experience
with the current version of ISIS-3D.

I don't know whether any of these databases is a relational
one.

I know that Chemical Design offers a 3D database which allows
to store chemical structures. Together with the structure some
distance informations are stored as a bit string which 
basically
specifies which distance ranges can be found for various
predefined atom groups (e.g. ionic groups, hydrogen bond 
donors
or acceptors etc.). This requires a conformational analysis to
be done in advance before the structure is stored in the 
database.
The idea is to make the "on the fly" conformational comparison
with a given query structure faster. Both UNITY and ISIS-3D
do the same job but store only one conformation and use a
fast algorithm for the same purpose. 

We tested Chemical Design's (CDL) software several years ago 
and
found many problems. However I meanwhile heard that the 
database tool (not the 2D/3D converter!) from CDL is said to 
be OK. 

regards, Herbert

-----------Herbert Koeppen, Boehringer Ingelheim KG, Med. 
Chem. Dept.-----------
-----------D-55216 Ingelheim, Germany, e-mail: 
[email-masked]

You can use CORINA to convert your data by an email
interface. See 
http://schiele.organik.uni-erlangen.de/services/3d.html

-- 
Dr. Wolf-D. Ihlenfeldt
Computer Chemistry Center, University of Erlangen-Nuernberg
Naegelsbachstrasse 25, D-91052 Erlangen (Germany)
Tel (+49)-(0)9131-85-6579  Fax (+49)-(0)9131-85-6566
---