Chemical Information Bulletin, Volume 43, Number 2, Summer 1991 Page: 30
52 p. ; 28 cm.View a full description of this periodical.
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9:55 AM
D. DOCKING LIGANDS INTO RECEPTORS:
THE TEST CASE OF a - CHYMOTRYPSIN.
K. Stewart, J. Bentley, and M. Cory, Division
of Organic Chemistry, Burroughs
Wellcome Co., 3030 Cornwallis Road, Research
Triangle Park, NC 27709.
As a test of 3D database searching methods,
structures of 103 ligands known to inhibit chymotrypsin
catalysis were automatically docked
into the active site of the enzyme by use of the
DOCK computer program (Kuntz et al, J. Med.
Chem. 31, 722, 1988). The goodness-of-fit was
evaluated according to an approximate LennardJones
potential scoring routine. Eight of the
top ten scoring molecules in the computerized
docking procedure had been previously reported
to be effective noncovalent inhibitors of chymotrypsin.
This agreement between the computer
predictions and experimental observations suggests
that the DOCK computer program may be
useful in evaluating other receptors for potential
binding ligands. Results with representative 3D
subsets of the Fine Chemicals Directory will
also be discussed.
10:20 AM
E. 3D-SHAPE FITTING AND 3D-DB SEARCHING
BY SPERM. V. J. van Geerestein, P.
D. J. Grootenhuis, C. A. G. Haasnoot, Computational
Medicinal Chemistry Group, Organon
International B. V., Oss, the
Netherlands.
In pharmaceutical research, the 3D-structure of
the studied enzyme or receptor is only in relatively
few occasions known is sufficient detail
to warrant searching 3D-DB's for molecules that
fit into the "lock", i.e. the binding site. Therefore,
a program called SPERM was developed
that is capable to search for molecules that fit
onto a certain "key". i.e. active compound.
SPERM implements an algorithm that has been
invented by Baldon (1990, J. Mol Graphics 7,
130-137). This algorithm has been optimised
and changed for application to large data sets.
To demonstrate the power of SPERM, we have
performed searches on netropsin (DNA minorgroove
binder) and daunomycin (DNA intercalator).
This choice was made because in these
cases also the "lock" (DNA) is known so that
we were able to verify our solutions by modeling
the molecular structure of the key and lock
complex. Recently, an alternative search was
performed by Grootenhuis et al. (1990, AntiCancer Drug Design 5, 237-242) on minor-groove
binders using the DOCK software which enablesus to compare the results and address the merits
of both methods. The principles of SPERM
will be presented and the results of the
netropsin and daunomycin searches will be discussed
in connection with the DOCK results.
10:45 AM
F. CHARACTERISTICS OF COMPUTER-GENERATED
3D AND RELATED MOLECULAR
PROPERTY DATA FOR CAS REGISTRY
SUBSTANCES. William Fisanick, Kevin P.
Cross, Andrew Rusinko, Chemical Abstracts
Service, P.O. Box 3012, Columbus,
OH 43210.
Chemical Abstracts Service is exploring approaches
for similarity searching, including
"fuzzy-match" searching, on CAS Registry substances.
Approaches for such substance
searching on 3D data and related molecular
property data hare being investigated. As the
first part of this effort, the 3D data have been
derived from the 3D coordinates generated by
the CONCORD program for sample files of Registry
substances, including a file of ring system
"framework" substances. In addition, molecular
property data such as atom charges have been
derived from the corresponding 3D data via
computational chemistry programs. Experimental
software has been developed to identify
and/or generate various characteristics for the
sample files of 3D and property data. Included
are 3D structural fragments, flexibility and shape
features, topographic indices, property features,
etc. The results of an analysis of these data
characteristics will be used in design of screening
and other aspects of search procedures.
11:10 AM
G. MEASURES OF 3D SHAPE SIMILARITY.
Paul G. Mezey, Director, Mathematical
Chemistry Research Unit, Department of
Chemistry and Department of Mathematics,
University of Saskatchewan, Saskatoon,
S7N OWO Canada.
Non-visual, numerical descriptors and measures
for the quantification of the three-dimensional
(3D) shapes of formal molecular bodies
and the associated measures for 3D shape similarity
have been developed, based on a topological
analysis of formal molecular bodies
represented by the 3D molecular electronic
charge distribution, or electrostatic potential or
simple fused-sphere van der Waals surfaces ordot representations. The most essential 3D
shape information is extracted by treating geo30 CHEMICAL INFORMATION BULLETIN
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American Chemical Society. Division of Chemical Information. Chemical Information Bulletin, Volume 43, Number 2, Summer 1991, periodical, Summer 1991; Philadelphia, Pennsylvania. (https://digital.library.unt.edu/ark:/67531/metadc5653/m1/32/: accessed April 25, 2024), University of North Texas Libraries, UNT Digital Library, https://digital.library.unt.edu; .