Quantitative structure-activity relationships combinatorial libraries

Quantitative Structure-Activity Relationship models are used increasingly in chemical data mining and combinatorial library design [5, 6]. For example, three-dimensional (3-D) stereoelectronic pharmacophore based on QSAR modeling was used recently to search the National Cancer Institute Repository of Small Molecules [7] to find new leads for inhibiting HIV type 1 reverse transcriptase at the nonnucleoside binding site [8]. A descriptor pharmacophore concept was introduced by us recently [9] on the basis of variable selection QSAR the descriptor pharmacophore is defined as a subset of... 

Keywords Combinatorial library design Quantitative structure - activity relationships Evolutionary algorithms Genetic algorithms Genetic programming... 

The purpose of the final section of this chapter is to review the practical applications of molecular enumeration and to give the reader interested in any of these applications pointers to relevant codes and techniques. In particular, the numbers of isomers for a specific molecular series are given, popular structure elucidation codes are reviewed, computed-aided structure elucidation successes are surveyed, and the connections between structure enumeration and combinatorial library design are established. The field of molecular design with inverse quantitative structure activity relationship is also reviewed. We conclude the chapter outlining future research directions. 

Bohl, M., Dunbar, J.B., GiSbrd, E.M., Heritage, T, Wild, D.J., Willett, P., and Wilton, D.J. (2002) Scaffold searching automated identification of similar ring systems for the design of combinatorial libraries. Quantitative Structure-Activity Relationships, 21, 590-597. 

Debnath AK (2006) Quantitative structure-activity relationship (QSAR)—a versatile tool in drug design. In Ghose AK, Viswanadhan VN (eds) Combinatorial library design and evaluation principles, software tools, and applications. Mercel Dekker Inc, New York... 

Combinatorial Chemistry Combinatorial Libraries Structure-Activity Analysis Combinatorics of Small Molecular Structures Competitive Molecular Field Analysis (CoM-FA) Drug Design Molecular Docking and Structure-based Design Quantitative Structure-Activity Relationships in Drug Design Quantitative Structure-Property Relationships (QSPR). 

In general, the described techniques provide an effective, flexible, and relatively fast solution for library design based on analysis of bioscreening data. The quantitative relationships, based on the assessment of contribution values of various molecular descriptors, not only permit the estimation of potential biological activity of candidate compounds before synthesis but also provide information concerning the modification of the structural features necessary for this activity. Usually these techniques are applied in the form of computational filters for constraining the size of virtual combinatorial libraries and... 

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