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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. April 2003, Volume 2, Number 4, 274-287 |
Three Dimensional Receptor Surface Model of Octopaminergic
Agonists for the Locust Neuronal Octopamine Receptor
Akinori Hirashima, Eiichi Kuwano, and Morifusa Eto
Internet Electron. J. Mol. Des. 2003, 2, 274-287
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Abstract:
In drug discovery, it is common to have measured
activity data for a set of compounds acting upon a
particular protein but not to have knowledge of the
three-dimensional structure of the protein active site. In the
absence of such three-dimensional information, one can
attempt to build a hypothetical model of the receptor site
that can provide insight about receptor site
characteristics. Such a model is known as a receptor
surface model (RSM), which provides compact and
quantitative descriptors that capture three-dimensional
information about a putative receptor site. All
computational experiments were conducted with Cerius2
3.8 quantitative structure-activity relationship (QSAR)
environment from Accelrys on a Silicon Graphics O2,
running under the IRIX 6.5 operating system. Multiple
conformations of each molecule were generated using the
Boltzmann Jump as a conformational search method. The
QSAR of a set of 60 octopamine (OA) agonists against
receptor 3 in locust nervous tissue was analyzed using
RSM. Three-dimensional energetic descriptors were
calculated from RSM/ligand interaction and these
three-dimensional descriptors were used in the QSAR analysis.
The predictive character of the QSAR was further
assessed using 10 OA agonists as test molecules. An
RSM was generated using some subset of the most active
structures and the results provided useful information in
the characterization and differentiation of the OA
receptor.
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