Molecular similarity/diversity methods

A powerful extension to the potential pharmacophore method has been developed, in which one of the points is forced to contain a special pharmacophore feature, as illustrated in figure 4. All the potential pharmacophores in the pharmacophore key must contain this feature, thus making it possible to reference the pharmacophoric shapes of the molecule relative to the special feature. This gives an internally referenced or relative measure of molecular similarity/diversity. The special feature can be assigned to any atom-type or site-point, or to special dummy atoms, such as those added as centroids of privileged substructures [7, 10]. With one of the points being reserved for this special feature, it would seem even more necessary to use the 4-point definition to capture enough of the... 

A special case of cell-based methods is a diversity measure proposed for binary fingerprints. Unlike continuous descriptors, binary descriptors such as structural keys and hashed fingerprints can be compared using fast binary operations to give rapid estimates of molecular similarity, diversity, and complementarity. The most common example of a diversity measure applied to binary descriptors is the binary union (inclusive or ). This can be exploited in a number of different ways elegant examples can be found in the following references. ... 

J S, I Morize, P R Menard, D L Cheney, C Hulme and R F Labaudiniere 1999. New 4-Point irmacophore Method for Molecular Similarity and Diversity Applications Overview of the thod and Applications, Including a Novel Approach to the Design of Combinatorial iraries Containing Privileged Substructures. Journal of Medicinal Chemistry 42 3251-3264. 

Mason JS, Morize 1, Menard PR, Cheney DL, Hulme C, Labaudiniere RF. New 4-point pharmacophore method for molecular similarity and diversity applications Overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures. I Med Chem 1999 42 3251-64. 

Evaluation of Molecular Similarity and Molecular Diversity Methods Using Biological Activity Data... 

This chapter reviews the techniques available for quantifying the effectiveness of methods for molecular similarity and molecular diversity, focusing in particular on similarity searching and on compound selection procedures. The evaluation criteria considered are based on biological activity data, both qualitative and quantitative, with rather different criteria needing to be used depending on the type of data available. 

The concepts of molecular similarity (1-3) and molecular diversity (4,5) play important roles in modern approaches to computer-aided molecular design. Molecular similarity provides the simplest, and most widely used, method for virtual screening and underlies the use of clustering methods on chemical databases. Molecular diversity analysis provides a range of tools for exploring the extent to which a set of molecules spans structural space, and underlies many approaches to compound selection and to the design of combinatorial libraries. Many different similarity and diversity methods have been described in the literature, and new methods continue to appear. This raises the question of how one can compare different methods, so as to identify the most appropriate method(s) for some particular application this chapter provides an overview of the ways in which this can be carried out, illustrating such comparisons by,... 

Chemoinformatics Concepts, Methods, and Tools for Discovery begins with an elaborate theoretical discussion of the concept of molecular similarity by Maggiora Shanmugasundaram that is one of the origins and cornerstones of chemoinformatics as we understand it today. Chapter 2 by Willett follows up on this theme and extends the discussion to molecular diversity, a related... 

Abstract Palladium-catalyzed oxidation reactions are among the most diverse methods available for the selective oxidation of organic molecules, and benzoquinone is one of the most widely used terminal oxidants for these reactions. Over the past decade, however, numerous reactions have been reported that utilize molecular oxygen as the sole oxidant. This chapter outlines the fundamental reactivity of benzoquinone and molecular oxygen with palladium(O) and their catalyst reoxidation mechanisms. The chemical similarities... 

In this chapter, we will give a brief introduction to the basic concepts of chemoinformatics and their relevance to chemical library design. In Section 2, we will describe chemical representation, molecular data, and molecular data mining in computer we will introduce some of the chemoinformatics concepts such as molecular descriptors, chemical space, dimension reduction, similarity and diversity and we will review the most useful methods and applications of chemoinformatics, the quantitative structure-activity relationship (QSAR), the quantitative structure-property relationship (QSPR), multiobjective optimization, and virtual screening. In Section 3, we will outline some of the elements of library design and connect chemoinformatics tools, such as molecular similarity, molecular diversity, and multiple objective optimizations, with designing optimal libraries. Finally, we will put library design into perspective in Section 4. 

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