Advances in diversity profiling and combinatorial series design

Dimitris K. Agrafiotis, James C. Myslik, F. Raymond Salemme
3-Dimensional Pharmaceuticals, Inc., 665 Stockton Drive, Exton, PA 19341, U.S.A.

Abstract
Rapid advances in synthetic and screening technology have recently enabled the simultaneous synthesis and biological evaluation of large chemical libraries containing hundreds to tens of thousands of compounds, using molecular diversity as a means to design and prioritize experiments. This paper reviews some of the most important computational work in the field of diversity profiling and combinatorial library design, with particular emphasis on methodology and applications. It is divided into four sections that address issues related to molecular representation, dimensionality reduction, compound selection, and visualization.

Keywords
analog design, combinatorial chemistry, experimental design, high throughput screening, QSAR, series design, similarity