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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. August 2006, Volume 5, Number 8, 431-446 |
Application of a Fragment-based Model to the Prediction of
the Genotoxicity of Aromatic Amines
Mose' Casalegno, Emilio Benfenati, and Guido Sello
Internet Electron. J. Mol. Des. 2006, 5, 431-446
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Abstract:
Aromatic amines are well known mutagenic compounds,
and their toxic effects have been thoroughly studied, thus
making them a good test dataset for computational models.
We developed a general approach to model compound
toxicity, particularly to aquatic organisms. The model uses
only diatomic fragments to estimate the compound
biological response. We are now going to apply this model
to a 95 compound dataset of aromatic amines to predict
their genotoxicity. In particular, the computed activities are
compared to the Salmonella mutagenicity tests that are a
sufficiently homogeneous set of experimental data. The
method used is very straightforward. Each molecule is
dissected into diatomic fragments; each of them is
represented by atom type, interatomic bond type, and
neighboring bond type. In this way, the variability of
atomic fragments is well represented and guarantees a good
representation of the molecular differences. Statistical
analysis uses both standard multilinear regression and
neural network analyses. The initial dataset has been
analyzed several times, using both the complete dataset and
four partitions of this dataset in order to: (a) validate the
model; (b) discuss the meaning of the result from a
chemical viewpoint. The results are interesting because
they demonstrate that our modeling approach is of general
application and that the statistical analysis allows for the
identification of some hints on the molecular characteristics
that differentiate the biological activity of each compound.
This new application of our modeling approach
demonstrates that it could be used in several different
models and applications.
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