Similarity property principle

Similarity search appears as an extremely useful tool for computer-aided structure elucidation as well as for molecular design. Here the similarity property principle is involved. This may be stated as ... 

The similarity property principle states structurally similar molecules are expected to exhibit similar physical properties or biological activities. ... 

Following the similar structure - similar property principle", high-ranked structures in a similarity search are likely to have similar physicochemical and biological properties to those of the target structure. Accordingly, similarity searches play a pivotal role in database searches related to drug design. Some frequently used distance and similarity measures are illustrated in Section 8.2.1. 

To understand the "similar structure-similar property" principle... 

The similar property principle implies that the NNs of a bioactive reference structure are also likely to possess that activity. If we assume that the NNs are not just likely to be active but actually are active, then we can use GF to combine the results of similarity searches that use them as the reference structures, using the strategy summarized in Fig. 2. 

Key Words Chemical database compound selection library design molecular diversity molecular similarity neighborhood behavior similar property principle similarity searching. 

The basis for all of the evaluation techniques to be discussed here is what is commonly referred to as the similar-property principle, which was first stated explicitly by Johnson and Maggiora in their seminal 1990 book (1). The principle states that structurally similar molecules are expected to exhibit similar properties. It is clear that there are many exceptions to the principle as stated... 

This application of the similar property principle was pioneered by Adamson and Bush (25,26) and has since been very extensively applied. For example, Willett and Winterman used it in one of the first detailed comparisons of measures for similarity searching (27), and it also formed the basis for Brown and... 

We have noted the importance of the similar property principle, which would imply that a set of compounds exhibiting some degree of structural redundancy,... 

In the context of compound partitioning, it should also be considered that relationships between structural and biological similarity can differ significantly. Much of the current molecular similarity research is based on the fundamental, and rather intuitive, similar property principle (18), which states that compounds with similar structures should generally have similar biologically activity. On the other hand, it is well known that minute structural modifications of active com-... 

It should be noted that the general understanding of molecular similarity goes beyond simple structural similarity and extends to biological activity, in accord with the so-called Similar Property Principle (Johnson and Maggiora 1990) postulating that molecules having similar structures and properties should also exhibit similar activity... 

A theoretical foundation of molecular similarity analysis is the assumption of neighborhood behavior ,which refers to the tendency of molecules with globally similar structures to exhibit similar biological activity. The well-known similarity-property principle (SPP) of Johnson and Maggiora expresses this paradigm and promotes a holistic view of molecular structure and properties. Molecular similarity applications assume that chemical similarity can be related to biological activity in a meaningful manner. However, the success of this approach ultimately depends on the way molecular similarity is defined. 

The conceptual basis for similarity analysis is provided by the similarity-property principle that states that similar molecules have similar biological activity.This rather intuitive principle has been widely accepted and substantiated by a wealth of observations. The success of many similarity-based virtual screening calculations can only be rationalized on the basis of this principle. However, minor modifications in molecular structure can dramatically alter the biological activity of a small molecule. This situation is exploited in lead optimization elforts, but limits the potential of similarity methods. These considerations also suggest that there must be fundamental dilferences between the structure-activity relationships (SARs). Thus, difierent types of SARs are expected to critically determine the success of similarity methods and systematic SAR analysis helps to better understand on a case-by-case basis why similarity methods might succeed or fail. 

D similarity searching The motivation to perform 2D similarity searches follows from the similarity property principle. All compounds having a similarity above a certain threshold are retrieved from the database by 2D similarity searching. In most cases the similarity is calculated by one of the aforementioned similarity measures based on molecular fingerprints. Therefore, in the first step the fingerprint for the query structure is calculated. 

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