Concepts of Molecular Diversity

The concept of molecular diversity became important as high throughput science gained traction in screening and synthesis. The fundamental question to be answered is how many molecules (and specifically which molecules) are needed to cover chemical space such that an HTS campaign will find a lead... 

Eerguson, A.M., Clark, R.D., and Weinberger, L.E. Neighborhood behavior a useful concept for validation of molecular diversity descriptors. 

Martin YC, Kofron JL, Traphagen LM. (2002) Do Structurally Similar Molecules Have Similar Biological Activities /. Med. Chem. 45 4350-4358. Patterson DE, Cramer RD, Ferguson AM, Clark RD, Weinberger LE. (1996) Neighbourhood Behaviour A Useful Concept for Validation of Molecular Diversity Descriptors. /. Med. Chem. 39 3049-3059. 

L. E. (1996) Neighborhood behavior A useful concept for validation of molecular diversity. J. Med. Chem. 39, 3049-3059. 

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... 

M Johnsonand G. Maggiora, Concepts and plications of Molecular Diversity, J ohn Wiley Sons, New York, 1990. 

The concept of molecular complexity was introduced into chemistry only quite recently and is mainly based on the information content of molecules. Several different measures of complexity can be obtained according to the diversity of the considered structural elements such as atom types, bonds, connections, cycles, etc. The first attempts to quantify molecular complexity were based on the elemental composition of molecules later other molecular characteristics were considered such as the symmetry of molecular graphs, molecular branching, molecular cyclicity and centricity [Bonchev and Seitz, 1996]. 

The generally accepted understanding of molecular diversity is a quantitative description of dissimilarity between molecules in a given set of compounds. The exact interpretation of this concept, however, has created quite a heated debate in the scientific literature [24]. For example, Roth fervently advocated that... 

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