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Design and Prioritization of Plates for High-Throughput Screening Dimitris K. Agrafiotis* and Dmitrii N. Rassokhin
 

Summary: Design and Prioritization of Plates for High-Throughput Screening
Dimitris K. Agrafiotis* and Dmitrii N. Rassokhin
3-Dimensional Pharmaceuticals, Inc., 665 Stockton Drive, Exton, Pennsylvania 19341
Received December 31, 2000
A general algorithm for the prioritization and selection of plates for high-throughput screening is presented.
The method uses a simulated annealing algorithm to search through the space of plate combinations for the
one that maximizes some user-defined objective function. The algorithm is robust and convergent, and
permits the simultaneous optimization of multiple design objectives, including molecular diversity, similarity
to known actives, predicted activity or binding affinity, and many others. It is shown that the arrangement
of compounds among the plates may have important consequences on the ability to design a well-targeted
and cost-effective experiment. To that end, two simple and effective schemes for the construction of
homogeneous and heterogeneous plates are outlined, using a novel similarity sorting algorithm based on
one-dimensional nonlinear mapping.
I. INTRODUCTION
In recent years, combinatorial chemistry1 has enabled
pharmaceutical research companies to augment their chemi-
cal archives with hundreds of thousands of new compounds
of potentially broad pharmaceutical interest. In most cases,
combinatorial libraries are synthesized in 96-well plates in
the form of arrays, which comprise all possible combinations

  

Source: Agrafiotis, Dimitris K. - Molecular Design and Informatics Group, Johnson & Johnson Pharmaceutical Research and Development

 

Collections: Chemistry; Computer Technologies and Information Sciences