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Summary: Kolmogorov-Smirnov statistic and its
application in library design
Dmitrii N. Rassokhin and Dimitris K. Agrafiotis
3-Dimensional Pharmaceuticals, Inc., Exton, Pennsylvania, USA
After several years of frantic development, the dream of an "ide-
al" library remains elusive. Traditionally, combinatorial chemis-
try has been used primarily for lead generation, and molecular
diversity has been the method of choice for designing and prior-
itizing experiments. One aspect that often has been overlooked is
the drug likeness of the resulting collections. Recently, there have
been several attempts to quantify this concept and incorporate it
directly into the design process. This article demonstrates the
limitations of some conventional methodologies and proposes a
new paradigm for experimental design based on the principles of
multiobjective optimization. This method allows traditional design
objectives such as diversity or similarity to be combined with
secondary selection criteria in order to bias the selection toward
more pharmacologically relevant regions of chemical space. The
method is robust, general, and easily extensible, and it allows the
medicinal chemist to create designs that represent the best com-
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