Computational library design,

An Effective Stochastic Optimization Approach to Computational Library Design... 

In the context of general screening, computational library design involves the selection of a subset of compounds that are optimally diverse and representative of available classes of compounds, leading to a non-redundant chemical library for biological testing. Methods reported in the literature include... 

Although the above-mentioned aspects of computational library design are multifaceted and complex, they can be tackled systematically using a comprehensive library design tool that employs the principle of multicriterion... 

The methods of simulated annealing (26), genetic algorithms (27), and taboo search (29) are three of the most popular stochastic optimization techniques, inspired by ideas from statistical mechanics, theory of evolutionary biology, and operations research, respectively. They are applicable to our current problem and have been used by researchers for computational library design. Because SA is employed in this chapter, a more-detailed description of the (generalized) SA is given below. 

Computational library design process begins with reagent selections, followed by diversity analysis and virtual library enumeration, and ends with selection of a final set of molecular structures to be synthesized (Fig. 9.4). Two databases, Available Chemical Database (ACD) (2) and Chemicals Available for... 

We could say that it is enough to substitute the concept of dissimilarity with that of similarity in the previous section to determine the application of computational library design to focused libraries. In fact, the tools used to describe and to select among virtual... 

R.A. Lewis, S.D. Pickett, D.E. Qark. Computer-aided molecular diversity analysis and combinatorial library design, in Reviews in Computational Chemistry, Vol. 16, K.B. Opkowitz, D.B. Boyd (Eds.). Wiley-VCH, New York. 2000. pp. 8-51. 

W Zheng, SI Cho, A Tropsha. Rational combinatorial library design 1. Focus-2D A new approach to the design of targeted combinatorial chemical libraries. J Chem Inf Comput Sci 38 251-258, 1998. 

Sciences (JCICS) in an attempt to meet the needs of today s computational chemists. JCICS was becoming the most popular venue for computational chemists to publish work on combinatorial library designs (see Fig. 1.2 and Section 1.6 on the 1990s). 

The described computational tools provide interactive, fast, and flexible data visualizations of chemical data that help and even enhance the human thought processes. However, visualization alone is often inadequate when multiple data points must be considered. A number of data mining methods that seek to identify significant relationships in large multidimensional databases are now being used for library design. 

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... 

Schuffenhauer A, Zimmermann J, Stoop R,van derVyver JJ, Lecchini S, Jacoby E. An ontology for pharmaceutical ligands and its application for in silico screening and library design. J Chem Inf Comput Sci 2002 42 947-55. 

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